CA3186297A1

CA3186297A1 - Cannabinoid formulations for aerosol devices and methods thereof

Info

Publication number: CA3186297A1
Application number: CA3186297A
Authority: CA
Inventors: John Emilio William Lopez
Original assignee: Markham Biotech Inc
Current assignee: Markham Biotech Inc
Priority date: 2016-09-15
Filing date: 2016-09-15
Publication date: 2018-03-15
Also published as: CA2941961A1; CA2941961C

Abstract

A cannabinoid liquid formulation for producing an aerosol via an inhalable vaporizing device, and/or electronic cigarette comprising cannabinoids from about 0.5% to about 75%
cannabinoid concentration. Provided herein is a method of delivering cannabinoids to a user comprising operating an electronic cigarette to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising cannabinoids in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure 100 to 10 000 bar @
25 C, and/or < 25 bar @ 25 C, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.

Description

CANNABINOID FORMULATIONS FOR AEROSOL
DEVICES AND METHODS THEREOF
SUMMARY OF THE INVENTION
100011 Provided herein is a method of delivering cannabinoids to a user comprising operating an aerosol inhalation device, also known as "electronic cigarette" to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.

[0002] Provided herein is a method of delivering cannabinoids to a user comprising operating an electronic cigarette to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
100031 Provided herein is a method of delivering cannabinoid to a user comprising operating an electronic cigarette wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
[0004] Provided herein is a method of delivering cannabinoids to a user comprising providing an electronic cigarette to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
[0005] Provided herein is a method of delivering cannabinoids to the blood of a user, said method comprising providing an aerosol that is inhaled by the user from an electronic cigarette that comprises a cannabinoid formulation wherein providing the aerosol comprises the electronic Date Recue/Date Received 2023-01-12 cigarette heating the formulation thereby generating the aerosol, wherein the aerosol is effective in delivering a level of cannabinoid in the blood of the user that is at least 0.20ng/mL at about 1.5 minutes after a first puff of ten puffs of the aerosol, each puff taken at 30 second intervals.
10006.1 Provided herein is a cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C.
[0007] Provided herein is a cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10 000 bar at 25 C.
[00081 Provided herein is a cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point.
[00091 Provided herein is a cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.
[0010] Provided herein is a cannabinoid liquid foi ululation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C.
100111 Provided herein is a cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10 000 bar at 25 C.
[00121 Provided herein is a cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids Date Recue/Date Received 2023-01-12 are further characterized by a melting point < 160 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point.
100131 Provided herein is a cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.
100141 Provided herein is a cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids arc characterized by vapor pressure < 25 bar at 50 C.
[00151 Provided herein is a cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10 000 bar at 25 C.
[00161 Provided herein is a cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point.
100171 Provided herein is a cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids arc further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.
[00181 Provided herein is a use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.
100191 Provided herein is a use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a

3 Date Recue/Date Received 2023-01-12 biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10 000 bar at 25 C, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.
[0020] Provided herein is a use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.
100211 Provided herein is a use of a cannabinoid formulation for delivery of cannabinoid to the blood of a user from an electronic cigarette, wherein the cannabinoid formulation in the electronic cigarette is heated to form an aerosol which delivers a level of cannabinoid in the blood of the user that is at least 0.20 ng/mL at about 1.5 minutes after a first puff of ten puffs of the aerosol, each puff taken at 30 second intervals.
[0022] Provided herein is a use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid salt in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.
[0023] Provided herein is a cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.
[0024] Provided herein is a cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid

4 Date Recue/Date Received 2023-01-12 formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.
[00251 Provided herein is a cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.
100261 Provided herein is a cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 20- degree difference between the melting point and the boiling point;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.
100271 Provided herein is an electronic cigarette for generating an inhalable aerosol comprising:
a fluid storage compartment;
a heater; and a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C; a battery;
and a mouthpiece.
[00281 Provided herein is an electronic cigarette for generating an inhalablc aerosol comprising:
a fluid storage compartment;
a heater; and Date Recue/Date Received 2023-01-12 a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids arc characterized by vapor pressure of about 100 to 10000 bar at 25 C;
a battery; and a mouthpiece.
[00291 Provided herein is an electronic cigarette for generating an inhalable aerosol comprising:
a fluid storage compartment;
a heater; and a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point;
a battery; and a mouthpiece.
100301 Provided herein is an electronic cigarette for generating an inhalable aerosol comprising:
a fluid storage compartment;
a heater; and a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic.cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point;
a battery; and a mouthpiece.
[0031] Provided herein is a cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compai tment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C.
100321 Provided herein is a cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C.

Date Recue/Date Received 2023-01-12 [0033] Provided herein is a cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point.
100341 Provided herein is a cartridge in an electronic cigarette comprising a fluid storage compai unent, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.
[0035[ Provided herein is a kit comprising:
(a) an electronic cigarette for generating an inhalable aerosol comprising I. a device body comprising a cartridge receptacle;
11. a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C;
Ill, a heater;
IV. a battery; and V. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.
[0036] Provided herein is a kit comprising:
(a) an electronic cigarette for generating an inhalable aerosol comprising I. a device body comprising a cartridge receptacle;
II. a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C;
Ill. a heater;

Date Recue/Date Received 2023-01-12 IV. a battery; and v. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.
[0037] Provided herein is a kit comprising:
(a) an electronic cigarette for generating an inhalable aerosol comprising i. a device body comprising a cartridge receptacle;
II. a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point;
111. a heater;
IV. a battery; and V. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.
[0038] Provided herein is a kit comprising:
(a) an electronic cigarette for generating an inhalable aerosol comprising 1. a device body comprising a cartridge receptacle;
11. a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point;
a heater;
IV. a battery; and V. a mouthpiece; and Date Recue/Date Received 2023-01-12 (b) instructions for using the electronic cigarette to generate an inhalable aerosol.
= BRIEF DESCRIPTION OF THE DRAWINGS
[0039] A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are used, and the accompanying drawings of which:
[00401 Figure 1 illustrates results of heart rate data measured for 200 minutes from start of puffing. Y-axis is heart rate (bpm) and X-axis represent duration of the test (0 10 200 minutes);
[0041] Figure 2 illustrates results of heart rate data measured for 200 minutes from start of puffing. Y-axis is heart rate (bpm) and X-axis represents duration of the test (0 to 200 minutes);
100421 Figure 3 illustrates the calculated vapor pressures of various organic solvents relative to cannabinoids;
[0043] Figure 4 illustrates the pharmacokinctic profiles for seven test articles in a blood plasma study;
[0044] Figure 5 illustrates the comparison of Cmax and Tmax for six test articles in a blood plasma study;
[0045] Figure 6 illustrates the comparison of Cmax and AUC for six test articles in a blood plasma study;
[0046] Figure 7 depicts an example embodiment of an electronic cigarette having a fluid storage compartment comprising an embodiment cannabinoid formulation described herein;
and 10047] Figure 8 depicts an example embodiment of an electronic cigarette cartomizer having a fluid storage compartment, a heater, and comprising an embodiment cannabinoid formulation described herein.
DETAILED DESCRIPTION OF THE INVENTION
100481 Cannabinoids are chemical compounds and increase the heart rate when administered to an animal or individual. Cannabinoid transfer to an individual has been studied extensively, and research has substantiated that cannabinoids are medically beneficial in the treatment of anorexia, insomnia, nausea, pain relief, and associated with a feeling of physical and/or emotional satisfaction, in individuals. Cannabinoid administration decreased subjective ratings of pain in neuropathic populations, using a laboratory model of pain that has predictive validity for clinical efficacy of analgesics in non-pain populations. Some reports have posited that vaporized or aerosolized administrations are preferred due to the faster onset and shorter duration of action, reduced exposure to harmful pyrolytic compounds, and the ability for patients to titrate dosage to the desired effect. One non-limiting example of a known shortcoming of the traditional cannabis Date Recue/Date Received 2023-01-12 cigarette is exposure to tar. Cannabinoid vaporization and/or aerosolized administration is a new technique that avoids the production of irritating respiratory toxins by heating the cannabinoid formulation, described herein, to a temperature where active cannabinoid vapors form, but below the point of combustion where toxins are released.
10049] It has been discovered that some cannabinoid formulations provide pain relief and therapeutic benefits, in an individual superior to that of oral cannabinoid administration, and more comparable to the pain relief in an individual smoking a traditional cannabis cigarette.
The pain relief effect is consistent with an efficient transfer of cannabinoid to the lungs of an individual and a rapid rise of cannabinoid absorption in the plasma as shown, for non-limiting example, in Example 8, at least.
It has also been unexpectedly discovered herein that certain cannabinoid formulations provide greater pain relief, and satisfaction than other cannabinoid formulations, and such effect has been shown in blood plasma levels of example cannabinoid formulations herein, for non-limiting example, in Example 8, at least. These results show a difference in rate of cannabinoid uptake in the blood that is higher for some cannabinoid formulations aerosolized by an electronic cigarette than for other cannabinoid formulations, and likewise higher than oral cannabinoid formulations, while the peak concentration of the cannabinoid in the blood and total amount of cannabinoid delivered appears comparable to a traditional cannabis cigarette, and do not appear to vary significantly between the various cannabinoid formulations. Therefore, described herein are cannabinoid formulations for use in an electronic cigarette, or the like, that provide a general pain relief effect, therapeutic benefit, and/or satisfaction consistent with an efficient transfer of cannabinoid to the lungs of an individual and a rapid rise of cannabinoid absorption in the plasma.
Provided herein, therefore, are devices, formulation of cannabinoid, systems, cartomizers, kits and methods that are used to inhale an aerosol generated from a cannabinoid liquid formulation through the mouth or nose as described herein or as would be obvious to one of skill in the art upon reading the disclosure herein.
100501 Consistent with these satisfaction effects, it has unexpectedly been found herein that there is a difference between the Cmax (maximum concentration) and Tmax (time at which the maximum concentration is measured) when measuring blood plasma cannabinoid levels of cannabinoid formulations inhaled using a low temperature vaporization device, i.e.
electronic cigarette, as compared to the Cmax and Tmax (similarly measuring blood plasma cannabinoid levels) of a traditional cannabis cigarette. Also consistent with these satisfaction effects, it has unexpectedly been found herein that there is a difference between the Cmax (maximum concentration) and Tmax (time at which the maximum concentration is measured) when measuring blood plasma cannabinoid levels of cannabinoid formulations inhaled using a low temperature vaporization device, i.e. electronic cigarette, as compared to the Cmax and Tmax (similarly measuring blood plasma cannabinoid levels) of other cannabinoid formulations inhaled using a low temperature Date Recue/Date Received 2023-01-12 vaporization device, i.e. electronic cigarette. Additionally, it has unexpectedly been found that there is a difference between the rate of cannabinoid uptake in the plasma of users inhaling cannabinoid formulations using a low temperature vaporization device, i.e.
electronic cigarette, as compared to the rate of cannabinoid uptake in the plasma of users inhaling smoke of a traditional cannabis cigarette. Furthermore, it has unexpectedly been found that there is a difference between the rate of cannabinoid uptake in the plasma of users inhaling cannabinoid formulations using a low temperature vaporization device, i.e. electronic cigarette, as compared to the rate of cannabinoid uptake in the plasma of users taking other cannabinoid formulations.
100511 Thus, looking at oral cannabinoids as a source of cannabinoid in compositions used in administration, oral cannabinoid compositions' delivery of cannabinoids to blood when ingested is not necessarily comparable in blood plasma levels (Cmax and Tmax) to a traditional cannabis cigarette's cannabinoid delivery to blood when inhaled. Oral cannabinoid compositions' delivery of cannabinoids to blood when ingested is not necessarily comparable in blood plasma levels (Cmax and Tmax) to a cannabinoid formulation's cannabinoid delivery to blood when inhaled.
Oral cannabinoid compositions' delivery of cannabinoids to blood when ingested is not necessarily comparable in blood plasma levels when measuring the rate of cannabinoid uptake in the blood within the first 0-30 minutes to a traditional cannabis cigarette's cannabinoid delivery to blood when inhaled. Oral cannabinoid compositions' delivery of cannabinoids to blood when ingested necessarily is not comparable in blood plasma levels when measuring the rate of cannabinoid uptake in the blood within the first 0-30 minutes to a cannabinoid formulation's cannabinoid delivery to blood when inhaled.
[00521 Also consistent with these satisfaction effects, it has unexpectedly been found herein that while there appears to be comparable Cmax and Tmax values (measuring blood plasma cannabinoid levels) of cannabinoid formulations inhaled using a low temperature vaporization device, i.e.
electronic cigarette, as compared to the Cmax and Tmax (similarly measuring blood plasma cannabinoid levels) of a traditional cannabis cigarette, there is a demonstrable difference between the rate of cannabinoid uptake in the plasma of users inhaling certain cannabinoid formulations using a low temperature vaporization device, i.e. electronic cigarette, as compared to the rate of cannabinoid uptake in the plasma of users inhaling other cannabinoid formulations using a low temperature vaporization device, i.e.
electronic cigarette. It is also unexpected that while the Cmax and Tmax values are comparable to those of a traditional cannabis cigarette, (or are approaching that of a traditional cannabis cigarette), the rate of cannabinoid uptake in the plasma of blood of users is higher in certain cannabinoid formulations than that of the traditional cannabis cigarette. The cannabinoid formulations which demonstrate the quickest rate of cannabinoid uptake in the plasma were more preferred in satisfaction evaluations, and were rated more equivalent to cannabis cigarette satisfaction than the cannabinoid Date Recue/Date Received 2023-01-12 formulations showing the slowest rates of rise of cannabinoid in the subjects' blood plasma. In addition, increasing the concentration of the cannabinoid in the formulation may not necessarily impact the rate of absorption of cannabinoid in the blood (see, for non-limiting example Example 8, cannabinoid formulations tested in 45% and 30% concentrations).
100531 Thus, looking at all cannabinoid formulations used in e-cigarettes, some cannabinoid formulations delivered using an c-cigarette appear comparable in Cmax and Tmax values (measuring blood plasma cannabinoid levels), however, not all eannabinoids perform similarly to each other or to a traditional cannabis cigarette with respect to the rate of cannabinoid uptake in the blood at early time periods (0-30 minutes). These results are unexpected. Cannabinoid formulations made using organic solvents having a Vapor Pressure between 10 to 10000 bar @ 25 C, or Vapor Pressure <
25 bar @ 50 C, or a Vapor Pressure from 10 to 10000 bar @ 25 C, or a Vapor Pressure from 100 to 10000 bar @ 25 C, a Vapor Pressure between 100 and 10000 bar @ 25 C
appear to have a higher rate of cannabinoid uptake in the blood at early time periods (0-5 minutes, 0-10 minutes, 0-15 minutes, 0-30 minutes for non-limiting example) than other cannabinoid formulations, however, they also provide pain relief, therapeutic benefit, and satisfaction comparable to a traditional cannabis cigarette or closer to a traditional cannabis cigarette (as compared to oral cannabinoid formulations or as compared to other cannabinoid formulations).
For non-limiting example, organic solvents that meet one or more criteria of the prior sentence include propane, butane, pcntanc, and CO2. Cannabinoid formulations made using organic solvents that have a difference between boiling point and melting point of at least 15 C, and a boiling point greater than -165 C, and a melting point less than 55 C appear to have a higher rate of cannabinoid uptake in the blood at early time periods (0-1.5 minutes, 0-2 minutes, 0-3 minutes, 0-4 minutes for non-limiting example) than other cannabinoid formulations, however, they also provide satisfaction comparable to a traditional cigarette or closer to a traditional cigarette (as compared to oral eannabinoid formulations or as compared to other cannabinoid formulations). For non-limiting example, organic solvents that meet the criteria of the prior sentence include propane, butane, pentane, and CO2. Cannabinoid formulations made using organic solvents that have a difference between boiling point and melting point of at least 15 C, ande boiling point at most 300 C less than operating temperature, and a melting point at least 20 C
lower than operating temperature appear to have a higher rate of cannabinoid uptake in the blood at early time periods (0-1.5 minutes, 0-2 minutes, 0-3 minutes, 0-4 minutes for non-limiting example) than other cannabinoid formulations, however, they also provide satisfaction comparable to a traditional cannabis cigarette or closer to a traditional cannabis cigarette (as compared to oral cannabinoid formulations or as compared to other cannabinoid formulations).
Operating temperature can be about 75 C to about 325 C, 100 C to 300 C, or about 200 C, about 150 C to about 250 C, 180C to 220 C, about 180 C to about 220 C, 185 C
to 215 C, Date Recue/Date Received 2023-01-12 about 185 C to about 215 C, about I90 C to about 210 C, 190 C to 210 C, 195 C
to 205 C, or about I95 C to about 205 C. For non-limiting example, organic solvents that meet the criteria of the prior sentence include propane, butane, pentane, and CO2. Combinations of these criteria for preference of certain cannabinoid formulations are contemplated herein.
[0054] Other reasons for excluding certain organic solvents from formulations may be unrelated to the rate of cannabinoid uptake, however. For example, an organic solvent may be inappropriate for use with the device materials (corrosive or otherwise incompatible). An organic solvent may be inappropriate for use in inhalation or for toxicity reasons - thus not be compatible for human consumption, ingestion, or inhalation (depending on the embodiment of the composition). An organic solvent that is bitter or otherwise bad-tasting may also provide a reason for exclusion, in some embodiments. Organic solvents that oxidize at room temperature or at operating temperature may be inappropriate for certain embodiments, as this indicates a decomposition or reaction or instability that may be undesirable in the formulation. Decomposition of organic solvents at room or operating temperatures may also indicate that the organic solvent is inappropriate for use in the embodiment formulations. For example, organic solvents that decompose at 175 C, or decomposes at 140 C, for a device operating at 200 C, may not be appropriate. Organic solvents that have poor solubility in the composition constituents may be inappropriate for use in certain embodiments of the compositions herein. For example, cannabinoids with a composition of organic solvents that will not produce a solution at a concentration of 0.5%(w/w) cannabinoid or higher in propylene glycol (PG) or vegetable glycerin (VG) or any mixture of PG and VG at ambient conditions. As used herein, weight percentage (w/w) refers to the weight of the individual component over the weight of the total formulation.
100551 As used in this specification and the claims, the singular forms "a,"
"an," and "the" include plural referents unless the context clearly dictates otherwise.
[0056] The term "organic solvent" as used herein, refers to an organic compound with solvent properties.
A non-limiting example of common organic solvents are the alkanes, which are hydrocarbons with no carbon __ carbon double or triple bonds.
[0057] The term "electronic cigarette" or "e-cigarette" or "aerosol inhalation device" or "low temperature vaporization device" as used herein, refers to an electronic inhaler that vaporizes a liquid solution into an aerosol mist, simulating the act of cannabis smoking.
The liquid solution comprises a formulation comprising cannabinoids. There are many electronic cigarettes which do not resemble conventional cigarettes at all. The amount of cannabinoid contained can be chosen by the user via the inhalation. In general, an electronic cigarette contains three essential components: a plastic cartridge that serves as a mouthpiece and a reservoir for liquid, an "atomizer" that vaporizes the liquid, and a battery. Other embodiment electronic cigarettes include a combined atomizer and reservoir, called a "cartomizer" that may or may not be disposable, a mouthpiece that may be Date Recue/Date Received 2023-01-12 integrated with the cartomizer or not, and a battery.
[0058] As used in this specification and the claims, unless otherwise stated, the term "about" refers to variations of 1%, 2%, 3%, 4%, 5%, 10%, 15%, 25%, or 50% depending on the embodiment.
[0059] Suitable carriers (e.g.., a liquid solvent) for the cannabinoids described herein include a medium in which a cannabinoid is soluble at ambient conditions, such that the cannabinoid does not form a solid precipitate. Examples include, but are not limited to, vegetable glycerin, glycerol, propylene glycol, trimethylene glycol, water, ethanol and the like, as well as combinations thereof. In some embodiments, the liquid carrier comprises 0% to 100% of propylene glycol and 100% to 0% of vegetable glycerin. In some embodiments, the liquid carrier comprises 10% to 70% of propylene glycol and 90% to 30% of vegetable glycerin. In some embodiments, the liquid carrier comprises 20% to 50% of propylene glycol and 80% to 50% of vegetable glycerin. In some embodiments, the liquid carrier comprises 30% propylene glycol and 70%
vegetable glycerin. In some embodiments, the liquid carrier comprises 50% propylene glycol and 50%
vegetable glycerin.
[0060] The formulations described herein vary in concentration. In some formulations, a dilute concentration of the cannabinoids in the carrier is utilized. In some formulations, a less dilute concentration of the cannabinoids in the carrier is utilized. In some formulations the concentration of cannabinoids in the cannabinoid formulation is about 1% (w/w) to about 75%
(w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is about 1% (w/w) to about 50% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is about 1% (w/w) to about 35% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is about I% (w/w) to about 25%
(w/w). In some embodiments the concentration of cannabinoids in the cannabinoid formulation is about 1% (w/w) to about 15% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is about 4% (w/w) to about 12% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is about 4% (w/w). In some embodiments the concentration of cannabinoids in the cannabinoid formulation is about 2%
(w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 1% (w/w) to 25% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 1% (w/w) to 20% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 1% (w/w) to 18% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 1% (w/w) to 15% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 4% (w/w) to 12% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 4% (w/w). In some formulations the concentration of cannabinoids in the cannabinoid formulation is 2% (w/w).
In some formulations, a less dilute concentration of one cannabinoid is used in conjunction with a Date Recue/Date Received 2023-01-12 more dilute concentration of a second cannabinoid. In some formulations, the concentration of cannabinoids in the first cannabinoid formulation is about 1% to about 50%, and is combined with a second cannabinoid formulation having a concentration of cannabinoid therein from about 1% to about 50% or any range or concentration therein. In some formulations, the concentration of cannabinoids in the first cannabinoid formulation is 1% to 25%, and is combined with a second cannabinoid formulation having a concentration of cannabinoids therein from 1%
to 25% or any range or concentration therein. As used with respect to concentrations of cannabinoids in the cannabinoid formulations, the term "about" refers to ranges of 0.05% (i.e. if the concentration is about 20%, the range is 19.95%-20.05%), 0.1 (i.e. if the concentration is about 20%, the range is 19.90%-20.10%), 0.25 (i.e. if the concentration is about 20%, the range is 19.75%-20.25%), 0.5 (i.e. if the concentration is about 20%, the range is 19.5%-20.5%), or 1 (i.e.
if the concentration is bout 20%, the range is 19%-21%), depending on the embodiment.
[00611 Cannabinoids are extracted by the introduction of a suitable organic solvent. In some formulations provided herein, suitable organic solvents are alkanes. Examples of alkanes disclosed herein are methane, ethane, propane, butane, pentane, hexane, heptanc, octane, nonane, decane, CO2 and the like. In some formulations provided herein, the organic solvents used herein is butane.
Cannabinoids are formed from the introduction of an organic solvent to cannabis. In some formulations provided herein, the stoichiometric ratios of the cannabis to organic solvent (cannabis:organic solvent) are 1:10, 1:11, 1:12, 1:13, 2:21, 2:23, 2:25, 3:31, 3:32, 3:34, 3:35, 3:37, 3:38, 4:41, 4:42, 4:43, 4:45, 4:46, 4:47, 4:49, 4:50, 5:51, 5:52, 5:53, 5:54,

5:56, 5:57, 5:58, 5:59, 5:61, 5:62, 5:63, or 5:64. In some formulations provided herein, the stoichiometric ratios of the cannabis to organic solvent are 1:9, 1:8, 1:7, 1:6, or 1:5 (cannabis:organic solvent).
[0062] Cannabinoids are a class of diverse chemical compounds that act on cannabinoid receptors in cells that represses neurotransmitter release in the brain. Ligands for these receptor proteins include the endocannabinoids (produced naturally in the body by animals), the phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (manufactured artificially). For non-limiting example the most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and cannabidiol (CBD), another major constituent of the plant. There are at least 125 different cannabinoids isolated from cannabis, exhibiting varied effects. Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally related to THC, the nonclassical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolincs, and arylsulfonamides, as well as cicosanoids related to cndocannabinoids.
[0063] Cannabinoid formulations may be formed by introducing a suitable organic solvent to cannabis, purging the organic solvent out of the neat mixture at ambient temperature or at elevated Date Recue/Date Received 2023-01-12 =
temperature, and then diluting the cannabinoid extract with a carrier mixture, such as a mixture of propylene glycol and glycerin. In some embodiments, the suitable organic solvent is completely purged from the cannabinoid extract prior to dilution. The suitable organic solvent may not completely purge from the cannabinoid extract prior to dilution. The addition of the suitable organic solvent to the cannabis to form a neat mixture may cause an endothermic reaction. The addition of the suitable organic solvent to the cannabis to form a neat mixture may be conducted at 15 C. The addition of the suitable organic solvent to the cannabis to form a neat mixture may be conducted at 50 C. The neat mixture may be warmed/cooled to ambient temperature prior to dilution. The dilution may be carried out at elevated temperature.
[0064] Cannabinoid formulations may be prepared by combining cannabinoid extract and a suitable organic solvent in a carrier mixture, such as a mixture of propylene glycol and glycerin. The mixture of cannabinoid extract and a first carrier mixture is combined with a mixture of a suitable organic solvent in a second carrier mixture. In some embodiments, the first and second carrier mixtures are identical in composition. In some embodiments, the first and second carrier mixtures are not identical in composition. In some embodiments, heating of cannabinoid/organic solvent/carrier mixture is required to facilitate complete dissolution.
[00651 In some embodiments, cannabinoid formulations may be prepared and added to a solution of 3:7 ratio by weight of propylene glycol (PG)/vegetable glycerin (VG), and mixed thoroughly. While described herein as producing I Og of each of the formulations, all procedures noted infra are scalable. Other manners of formulation may also be employed form the formulations noted infra, without departing from the disclosure herein, and as would be known to one of skill in the art upon reading the disclosure herein.
[0066] The optimal cannabinoid formulation may be determined by the vapor pressure of the constituent organic solvent. In some embodiments, the cannabinoid formulations comprise an organic solvent with a vapor pressure that is similar to the vapor pressure of other cannabinoid formulations. In some embodiments, the cannabinoid formulations arc formed from an organic solvent with a vapor pressure that is similar to the vapor pressure of other cannabinoid formulations at the heating temperature of the device. Figure 3 illustrates this trend.
Cannabinoids formed from cannabis and propane; cannabis and butane; or cannabis and CO2 are concentrated extracts that produce a satisfaction in an individual user consistent with efficient transfer of cannabinoid and a rapid rise in cannabinoid plasma levels. This pattern may be due to the mechanism of action during heating of the cannabinoid formulation. The cannabinoid may disassociate at, or just below, the heating temperature of the device, resulting in a mixture of cannabinoid and the individual organic solvent. At that point, if both the cannabinoid and organic solvent have similar vapor pressures, they may aerosolize at the same time, giving rise to a transfer of both cannabinoid and the constituent organic solvent to the user.

Date Recue/Date Received 2023-01-12 [0067] The cannabinoid liquid formulation for generating an inhalable aerosol upon heating in an electronic cigarette may comprise a cannabinoid in a biologically acceptable liquid carrier;
wherein the organic solvent used to form said cannabinoids are characterized by a vapor pressure between 100 to 10000 bar at 25 C. In some embodiments, the organic solvent used to form the cannabinoid is characterized by vapor pressure less than 25 bar at 50 C. In some embodiments, the organic solvent used to form the cannabinoid is characterized by vapor pressure between 10 - 10000 bar at 25 C.
[0068] Different cannabinoid formulations produced varying degrees of satisfaction in an individual. In some embodiments, the concentration of the cannabinoid affected satisfaction, such that increased concentration was more satisfying as compared to less concentration. The cannabinoid formed may be highly concentrated. The cannabinoid formed may be less concentrated.
The cannabinoid may exist in more than one concentration state, e.g., an equilibrium of low and highly concentrated cannabinoids. The extent of concentration of the cannabinoid molecule may be dependent upon the stoichiometric ratio of cannabis:organic solvent used in the cannabinoid formation reaction.
The extent of concentration of the cannabinoid molecule may be dependent upon the solvent. The extent of concentration of the cannabinoid molecule may be unknown. In some embodiments, highly concentrated cannabinoid formulations produced a high degree of satisfaction in the user.
The reason for this trend may be explained by a mechanism of action wherein the cannabinoid is first separated prior to transfer to the vapor with the constituent acceptable liquid carrier and then retained and stabilized after by the organic solvent going down stream to the lungs of the user. It may be possible to modify the acceptable liquid carrier, thus resulting in better transfer efficiency.
In addition, the lack of satisfaction of some cannabinoids indicates that a second factor may be important. A cannabinoid may be best performing when it is at its optimal extent vaporization, depending on the formulation. For example, cannabinoids with a cannabinoid ratio of 1:2 (cannabinoid:acceptable liquid carrier), may deliver less satisfaction to the user than the one containing same amount of cannabinoids but only half amount of acceptable liquid carrier, i.e.
cannabinoid:acceptable liquid carrier (1: 1). This may be explained as 1 mole of cannabinoids produces a formulation with 2 moles of acceptable liquid carrier. When there is not enough cannabinoid to associate with all the acceptable liquid carrier molecules, the cannabinoids left in the formulation may reduce the satisfaction, pain relief, and therapeutic benefits the formulation provides.
[0069] The flavor of the constituent organic solvent used in the extract formation may be a consideration in choosing the organic solvent. A suitable organic solvent may have minimal or no toxicity to humans in the concentrations used. A suitable organic solvent may be compatible with the electronic cigarette components it contacts or could contact at the concentrations used. That is, such organic solvent does not degrade or otherwise react with the electronic cigarette components Date Recue/Date Received 2023-01-12 it contacts or could contact. The odor of the constituent organic solvent used in the extract formation may be a consideration in choosing a suitable organic solvent. The concentration of the cannabinoid in the carrier may affect the satisfaction in the individual user.
In some embodiments, the flavor of the formulation is adjusted by changing the organic solvent. In some embodiments, the flavor of the formulation is adjusted by adding exogenous flavorants. In some embodiments, an unpleasant tasting or smelling organic solvent is used in minimal quantities to mitigate such characteristics. In some embodiments, exogenous pleasant smelling or tasting organic solvent is added to the formulation.
10070] Cannabinoid formulations may generate an inhalable aerosol upon heating in an electronic cigarette. The amount of cannabinoid or cannabinoid aerosol inhaled may be user- determined.
The user may, for example, modify the amount of cannabinoid or cannabinoids inhaled by adjusting inhalation strength.
100711 Formulations are described herein comprising two or more cannabinoids.
In some embodiments, wherein a formulation comprises two or more cannabinoids, each individual cannabinoid is formed as described herein.
100721 Cannabinoid formulations, as used herein, refer to a single or mixture of cannabinoids with other suitable chemical components used for c-cigarette, such as carriers, stabilizers, diluents, dispersing agents, suspending agents, thickening agents, and/or excipients. In certain embodiments, the cannabinoid formulation is stirred at ambient conditions for 20 minutes. In certain embodiments, the cannabinoid formulation is heated and stirred at 55C for 20 minutes. In certain embodiments, the cannabinoid formulation is heated and stirred at 90C for 60 minutes. In certain embodiments, the formulation facilitates administration of cannabinoid to an organism (e.g., lung).
[00731 The cannabinoids of cannabinoid formulations provided herein are either naturally occurring cannabinoids (e.g., from extract of cannabinoid containing species such as cannabis), or synthetic cannabinoids. In some embodiments, the cannabinoid is employed in relatively pure form (e.g., greater than about 80% pure, 85% pure, 90% pure, 95% pure, or 99 % pure). In some embodiments, the cannabinoid for cannabinoid formulation provided herein is "water Clear" in appearance in order to avoid or minimize the formation of tarry residues during the subsequent extract formation steps.
100741 Cannabinoid formulations used for c-cigarettes described herein, in some embodiments, have a cannabinoid concentration of about 0.5% (w/w) to about 80% (w/w), wherein the concentration is of cannabinoid weight to total solution weight, i.e. (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about I%
(w/w) to about 80%
(w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1% (w/w) to about 50% (w/w). In certain embodiments, cannabinoid Date Recue/Date Received 2023-01-12 formulations provided herein have a cannabinoid concentration of about 1%
(w/w) to about 35%
(w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 4% (w/w) to about 25% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1%
(w/w) to about 35%
(w/w), about 3% (w/w) to about 25% (w/w), or about 4% (w/w) to about 15%
(w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 0.5% (w/w) to about 10% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 0.5% (w/w) to about 5% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 0.5% (w/w) to about 4% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 0.5% (w/w) to about 3% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 0.5% (w/w) to about 2% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 0.5% (w/w) to about I% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1% (w/w) to about 10% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1% (w/w) to about 5%
(w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1% (w/w) to about 4% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1% (w/w) to about 3%
(w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 1% (w/w) to about 2% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 2% (w/w) to about 10% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 2% (w/w) to about 5% (w/w). In certain embodiments, cannabinoid formulations provided herein have a cannabinoid concentration of about 2% (w/w) to about 4%
(w/w). Certain embodiments provide a cannabinoid formulation having a cannabinoid concentration of about 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, or 90% (w/w), or more, including any increments therein.
Certain embodiments provide a cannabinoid formulation having a cannabinoid concentration of about 50% (w/w). Certain embodiments provide a cannabinoid formulation having a cannabinoid concentration of about 40% (w/w). Certain embodiments provide a cannabinoid formulation having a cannabinoid concentration of about 30% (w/w). Certain embodiments provide a Date Recue/Date Received 2023-01-12 cannabinoid formulation having a cannabinoid concentration of about 20% (w/w).
Certain embodiments provide a cannabinoid formulation having a cannabinoid concentration of about 10%
(w/w). Certain embodiments provide a cannabinoid formulation having a cannabinoid concentration of about 5% (w/w).
100751 The formulation further may comprise one or more flavorants.
10076] Thee suitable organic solvent for the cannabinoid formulation may have a vapor pressure <25 bar at 50 C and is non-corrosive to the electronic cigarette or is non-toxic to humans. In some embodiments, the suitable organic solvent for cannabinoid formation is selected from the aforementioned group.
100771 Thee suitable organic solvent for the cannabinoid formulation may have a vapor pressure of about 100 to 10000 bar at 25 C and is non-corrosive to the electronic cigarette or is non-toxic to humans.
In some embodiments, the suitable organic solvent for cannabinoid formation is selected from the aforementioned group.
[00781 Thee suitable organic solvent for the cannabinoid formulation may have a melting point <55 C, a boiling point> -165 C, at least a 15-degree difference between the melting point and the boiling point, and is non-corrosive to the electronic cigarette or is non-toxic to humans. In some embodiments, the suitable organic solvent for cannabinoid formation has a melting point at least 20 degrees lower than the operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, at least a 15-degree difference between the melting point and the boiling point, and is non-corrosive to the electronic cigarette or is non-toxic to humans; wherein the operating temperature is 200 C. In some embodiments, the suitable organic solvent for cannabinoid formation is selected from the aforementioned group.
100791 Thee suitable organic solvent for the cannabinoid formulation does not decompose at the operating temperature of the electronic cigarette. In some embodiments, the suitable organic solvent for cannabinoid formation does not oxidize at the operating temperature of the electronic cigarette. In some embodiments, the suitable organic solvent for cannabinoid formation does not oxidize at room temperature. In some embodiments, the suitable organic solvent for cannabinoid formation does not provide an unpleasant taste. In some embodiments, the suitable organic solvent for cannabinoid formation has good solubility in a liquid formulation for use in an electronic cigarette.
100801 Provided herein is an electronic cigarette 2 having a fluid storage compartment 4 comprising an embodiment cannabinoid formulation of any embodiment described herein within the fluid storage compartment described herein. An embodiment is shown in FIG. 7. The electronic cigarette 2 of FIG. 7 includes a mouth end 6, and a charging end 8. The mouth-end 6 includes a Date Recue/Date Received 2023-01-12 mouthpiece 10. The charging end 8 may connect to a battery or a charger or both, wherein the battery is within a body of the electronic cigarette, and the charger is separate from the battery and couples to the body or the battery to charge the battery. In some embodiments the electronic cigarette comprises a rechargeable battery within a body 14 of the electronic cigarette and the charge end 8 comprises a connection 12 for charging the rechargeable battery.
In some embodiments, the electronic cigarette comprises a cartomizer that comprises the fluid storage compartment and an atomizer. In some embodiments, the atomizer comprises a heater. In some embodiments the fluid storage compartment 4 is separable from an atomizer. In some embodiments the fluid storage compartment 4 is replaceable as part of a replaceable cartridge. In some embodiments the fluid storage compartment 4 is refillable. In some embodiments, the mouthpiece 10 is replaceable.
100811 Provided herein is a cartomizer 18 for an electronic cigarette 2 having a fluid storage compartment 4 comprising an embodiment cannabinoid formulation of any embodiment described herein within the fluid storage compartment described herein. The cartomizer 18 embodiment of FIG. 8 includes a mouth end 6, and a connection end 16. The connection end 16 in the embodiment of FIG. 8 couples the cartomizer 14 to a body of an electronic cigarette, or to a battery of the electronic cigarette, or both. The mouth end 6 includes a mouthpiece 10. In some embodiments, the cartomizer does not include a mouthpiece, and in such embodiments, the cartomizer can be coupled to a mouthpiece of an electronic cigarette, or the cartomizer can be coupled to a battery or body of an electronic cigarette, while the mouthpiece is also coupled to the battery or the body of the electronic cigarette. In some embodiments, the mouthpiece is integral with the body of the electronic cigarette. In some embodiments, including the embodiment of FIG.
8, the cartomizer 18 comprises the fluid storage compartment 4 and an atomizer (not shown). In some embodiments, the atomizer comprises a heater (not shown) Examples Example 1: Preparation of cannabinoid formulations 100821 Various cannabinoid formulations were prepared and added to a liquid carrier solution of 8:2 ratio by weight of propylene glycol (PG)/vegetable glycerin (VG), and mixed thoroughly. The examples shown below were used to make lOg of each of the formulations. All procedures are scalable.
100831 For example, in order to make cannabinoid formulations with a final cannabinoid equivalent concentration of 30% (w/w), the following procedures were applied to each individual formulation.
- Cannabinoid formulation: 8m1 liquid carrier was added to a beaker followed by adding 4g Date Recue/Date Received 2023-01-12 cannabinoid extract to the same beaker. The mixture was stirred at 55 C for 20 minutes until the eannabinoid extract was completely dissolved and an orange oily mixture was formed. The mixture was cooled down to ambient conditions, and the mixture was stirred until a visually homogenous formulation solution was achieved.
-Cannabinoid formulation can also be made by adding 4mL liquid carrier to a beaker followed by adding 4g cannabinoid extract and 4mL PGN G (8:2) solution to the same beaker.
The mixture was then stirred at 55 C for 20 minutes until a visually homogenous formulation solution was achieved with no undissolved cannabinoid extract. Cannabinoid formulation was made by adding 8mL liquid carrier to a beaker followed by adding 4g cannabinoid extract and 8mL PGN G (8:2) solution to the same beaker. The mixture was then stirred at 90 C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals.
- Cannabinoid formulation was made by adding 4mL liquid carrier to a beaker followed by adding 4g cannabinoid extract and 4mL PGN G (8:2) solution to the same beaker. The mixture was then stirred at 90 C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals.
- Cannabinoid formulation can also be made by adding 4mL liquid carrier to a beaker followed by adding 4g cannabinoid extract to the same beaker. The mixture was stirred at 90 C for 60 minutes until completely dissolved and an orange oily mixture was formed. The mixture was either cooled to ambient conditions or kept at 90 C when 4mL PGN G (8:2) solution was added.
The mixture was then stirred at 90 C until a visually homogenous formulation solution was achieved with no undissolved chemicals.
- Cannabinoid formulation was made by adding 4g cannabinoid to a beaker followed by adding 8mL PGN G (8:2) solution to the same beaker. The mixture was then stirred at ambient conditions for 10 minutes until a visually homogenous formulation solution was achieved.
100841 For example, in order to make cannabinoid formulations with a final cannabinoid equivalent concentration of 45% (w/w), the following procedures were applied to each individual formulation.
- Cannabinoid formulation: 6mL liquid carrier was added to a beaker followed by adding 6g cannabinoid extract to the same beaker. The mixture was stirred at 55 C for 20 minutes until completely dissolved and an orange oily mixture was formed. The mixture was cooled down to ambient conditions. and the blend was stirred until a visually homogenous formulation solution was achieved.
- Cannabinoid formulation can also be made by adding 4mL liquid carrier to a beaker followed by adding 6g cannabinoid extract and 2mL PGN G (8:2) solution to the same beaker.
The mixture was then stirred at 55 C for 20 minutes until a visually homogenous formulation solution was achieved Date Recue/Date Received 2023-01-12 with no undissolved chemicals.
- Cannabinoid formulation was made by adding 6mL PG to a beaker followed by adding 6g cannabinoid extract to the same beaker. The mixture was then stirred at 90 C
for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals.
- Cannabinoid formulation was made by adding 4mL liquid carrier to a beaker followed by adding 6g cannabinoid extract and 2mL PGN G (8:2) solution to the same beaker. The mixture was then stirred at 90 C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals.
- Cannabinoid formulation was made by adding melted 6g cannabinoid extract to a beaker followed by adding 4mL liquid carrier to the same beaker. The mixture was stirred at ambient conditions for 10 minutes, and an oily product was produced. The mixture was allowed to cool down to ambient temperature and 2mL PGN G (8:2) solution was added to the same beaker. The mixture was then stirred at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved.
- Cannabinoid formulation was made by adding 6mL liquid carrier to a beaker followed by adding 6g cannabinoid extract to the same beaker. The mixture was stirred at ambient conditions for 10 minutes, and oily product was produced. The mixture was allowed to remain at ambient temperature then the mixture was then stirred at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved.
100851 For example, in order to make cannabinoid formulations with a final cannabinoid equivalent concentration of 15% (w/w), the following procedures were applied to each individual formulation.
- Cannabinoid formulation: 4mL liquid carrier was added to a beaker followed by adding 2g cannabinoid extract to the same beaker. The mixture was stirred at 55 C for 20 minutes until completely dissolved and an orange oily mixture was formed. Thc mixture was cooled down to ambient conditions. 6mL PGN G (8:2) solution was added to the orange cannabinoid mixture and the blend was stirred until a visually homogenous formulation solution was achieved.
- Cannabinoid formulation can also be made by adding 10mL carrier liquid to a beaker followed by adding 2g cannabinoid extract to the same beaker. The mixture was then stirred at 55 C for 20 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals.
For example, in order to make cannabinoid formulations with a final cannabinoid equivalent concentration of 3.75% (w/w), the following procedures were applied to each individual formulation.
- Cannabinoid formulation: 1.5mL liquid carrier was added to a beaker followed by adding 0.5g Date Recue/Date Received 2023-01-12 cannabinoid extract to the same beaker. The mixture was stirred at 55 C for 20 minutes until completely dissolved and an orange oily mixture was formed. The mixture was cooled down to ambient conditions. 10mL PGN G (8:2) solution was added to the orange cannabinoid mixture and the blend was stirred until a visually homogenous formulation solution was achieved.
- Cannabinoid formulation can also be made by adding 11.5mL liquid carrier to a beaker followed by adding 0.5g cannabinoid extract to the same beaker. The mixture was then stirred at 55 C for 20 minutes until a visually homogenous formulation solution was achieved with no undissolved chemicals.
- Cannabinoid formulation was made by adding 11.5mL liquid carrier to a beaker followed by adding 0.5g cannabinoid extract to the same beaker. The mixture was then stirred at 90 C for 60 minutes until a visually homogenous formulation solution was achieved with no undissolved cannabinoid extract.
- Cannabinoid formulation was made by adding melted 0.5g cannabinoid extract to a beaker followed by adding 11,5mL liquid carrier to the same beaker. The mixture was stirred at ambient conditions for 10 minutes, and an oily product was produced. The mixture was allowed to remain at ambient temperature and the mixture was then stirred at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved.
- Cannabinoid formulation was made by adding 1.5mL liquid carrier to a beaker followed by adding 0.5g cannabinoid extract to the same beaker. The mixture was stirred at ambient conditions for 10 minutes, and an oily product was produced. The mixture was allowed to cool down to ambient temperature and 10mL PGN G (8:2) solution was added to the same beaker. The mixture was then stirred at ambient conditions for 20 minutes until a visually homogenous formulation solution was achieved.
100861 Various formulations comprising different cannabinoids can be prepared similarly, or different concentrations of the above-noted cannabinoid formulations or other cannabinoid formulations or other liquid carrier ratios of PG:VG can be prepared as one of skill in the art would know to do upon reading the disclosure herein.
100871 Various formulations comprising two or more cannabinoids can be prepared similarly in a solution of 8:2 ratio of propylene glycol (PG)/vegetable glycerin (VG). For example, lg (90% w/w cannabinoid) of cannabinoid CBD and lg (90% w/w cannabinoid) of cannabinoid THC are added to 10mL of PGN G solution, to achieve a 15% w/w cannabinoid formulation.
[00881 Also provided is another exemplary formulation. For example, 0.67g (90%
w/w cannabinoid) of cannabinoid CBD, 0.67g (90% w/w cannabinoid) of cannabinoid THC and 0.67 g (90% w/w cannabinoid) of cannabinoid CBN are added to 9mL of PGN G solution, to achieve a 15% w/w cannabinoid formulation.

Date Recue/Date Received 2023-01-12 Example 2: Heart rate study of cannabinoid solutions 100891 Exemplary formulations of cannabinoids, and a control of placebo were prepared and administered in similar fashion to an electronic cigarette to the human subjects. The formulations were designated as low dose (1.8%) cannabinoid, and high-dose (3.9%) cannabinoid.
100901 Baseline heart rate measurements were conducted immediately prior to the consumption of cannabinoids. Measurements were continuously taken at predetermined intervals up to 200 minutes. Final results were presented in FIG. 1.
[00911 FIG. 1 summarizes results from heart rate measurements taken for cannabinoid formulations. For ease of reference in reviewing FIG. 1, at the 60-minute time-point, from top to bottom (highest heart rate to lowest heart rate), the cannabinoid formulations are as follows:
high-dose cannabinoid, low-dose cannabinoid, and placebo. The test formulations comprising a cannabinoid cause a faster and more significant rise in heart rate than the placebo. The test formulations comprising a high dose cannabinoid also cause faster and more significant rise when compared with a low dose cannabinoid formulation with the same amount of cannabinoid by weight. In turn, the cannabinoids (e.g., CBD, or THC) prepared from the organic solvents having calculated vapor pressures between 100 to 10 000 bar at 25 C, or <25 bar @ 50 C cause a faster risc in heart rate than placebo. The cannabinoids prepared from the organic solvents also cause a more significant heart rate increase than placebo. Thus, other suitable cannabinoids formed by the organic solvents with the similar vapor pressure and/or similar boiling point may be used in accordance with the practice of the present invention.
Example 3: Satisfaction Study of Cannabinoid Solution via c-cigarette 1009211n addition to the heart rate study shown in Example 2, cannabinoid formulations were used to conduct a satisfaction study in 10 test participants. The test participant, an c-cigarette and/or traditional cigarette user, was required to have no cannabinoid intake for at least 24 hours before the test. The participants took 3puffs using an e-cigarette or electronic vaporization device over 5 minutes in each case, and then was asked to rate the level of physical and emotional satisfaction he or she felt on a scale of 0 - 5, with 0 being no physical or emotional satisfaction. The results indicated that all cannabinoid formulations performed well and/or better than a traditional cannabis cigarette.
[00931 Based on the Satisfaction Study, the cannabinoids formulations formed with organic solvents having vapor pressure ranges between 100 to 10 000 bar @ 25 C , or <25 bar C_/), 50 C provide more satisfaction than oral or a traditional cannabis cigarette.
Example 4: Test formulation 1 (TF1):
Date Recue/Date Received 2023-01-12 100941 A solution of cannabinoids in propylene glycol comprising: 1g (90% w/w) of cannabinoid extract and 2mL of propylene glycol - Total volume 3mL.
100951 Cannabinoid extract was added to the propylene glycol, and mixed thoroughly. In a 1:2 molar ratio the percentage of cannabinoids in the cannabinoid formulation by weight is given by: (1g I 3mL)90 = 30% (w/w).
Example 5: Test formulation 2 (TF2):
100961 A solution of cannabinoid in propylene glycol comprising lg (90% w/w) of cannabinoid extract was dissolved in ImL of propylene glycol and mixed thoroughly.
Example 6: Heart rate study of cannabinoid solutions via e-cigarette:
100971 Representative formulations (TF1 and TF2) were administered in similar fashion to an electronic cigarette to human subjects. The operating temperature of the e-cigarette is from about 75 C to about 325 C, or from about 100 C to about 300 C.
1000981The atomizer coils in both cases had a resistance of either: 0.9ohms, and the electronic vaporization device was set to 5V, resulting in 27.8W of power; or 0.2ohms, and the electronic vaporization device was set to the "variable wattage" setting thus allowing the atomizer coils no maintain a consistent temperature (250 C) throughout vaporization (P VA2/R) 1000991 Heart rate was measured in a 30-second interval for 200 minutes from start of puffing. Test participants took puffs ad libitum over 5 minutes in each case (solid line (highest peak): cannabis cigarette, dark dotted line (3rd highest peak): test formulation 1 (TF I - low-dose cannabinoid formulation), light dashed line (2" highest peak): test formulation 2 (TF2 - high-dose cannabinoid formulation). Comparison between cannabis cigarette, TF1, and TF2 is shown in FIG. 2.
1001001 It is clearly shown in FIG. 2 that the test formulation with high-dose cannabinoid (TF2) causes a faster rise in heart rate than low-dose cannabinoid (TF1).
Also, TF2 more closely resembles the rate of increase for a cannabis cigarette. Thus, other suitable cannabinoids that cause the similar effect may be used in accordance with the practice of the present invention. This experience of increased heart rate comparable to that of a traditional burned cannabis cigarette has not been demonstrated or identified in other electronic cigarette devices, nor has it been demonstrated or identified in low temperature cannabis vaporization devices that do not burn the cannabis.
[00101]In addition, the data appears to correlate well with the previous findings shown in FIG. 2.
1001021 As previously noted in the Satisfaction Study, the cannabinoid formulations with organic solvents having vapor pressures between 100 to 10 000 bar @ 25 C and/or <25 bar @ 50 C

Date Recue/Date Received 2023-01-12 provide more satisfaction than the rest, as noted in FIG. 3. Based on the findings herein, it was anticipated that these cannabinoid formulations having either:
a Vapor Pressure between 100- 10 000 bar @ 25 C, a Vapor Pressure > 25 bar @ 50 C, a difference between boiling point and melting point of at least 15 C, and a boiling point greater than -165 C, and a melting point less than 55 C, a difference between boiling point and melting point of at least 15 C, and a boiling point greater than -165 C, and a melting point less than 55 C, a difference between boiling point and melting point of at least 15 C, and a boiling point at most 300 C less than operating temperature, and a melting point at least 20 C lower than operating temperature, or a combination thereof produce one or more of the following effects:
1001031Tmax - Time to maximum blood concentration: Based on the results established herein, a user of an e-cigarette comprising the cannabinoid formulation will experience a comparable rate of physical and emotional satisfaction from using a formulation comprising a mixture of cannabinoids prepared with an appropriate organic solvent at least 1.2X to 3X
faster than baseline.
As illustrated in FIG. 1: cannabinoids from a low-dose cannabinoid formulation appears to generate a heartbeat that is nearly 1.2 times that of a normal heart rate for an individual approximately 10 minutes after the commencement of puffing; whereas the cannabinoid from a high-dose cannabinoid formulation appears to generate a heartbeat that is nearly 1.3 times that of a normal heart rate for an individual approximately 10 minutes after the commencement of puffing.
1001041 Again this would not be inconsistent with the data from FIG. 2, where the data illustrated that at approximately 10 minutes, the heart rate of test participants reached a maximum of 84-87 bpm with either a traditional cannabis cigarette or a cannabinoid formulation (TF2); whereas those same participants heart rates only reached a maximum of approximately 78 bpm at approximately minutes with a cannabinoid formulation (TF1); also a difference in effect of 1.2 times greater with administration of cannabinoid formulations (and traditional cannabis cigarettes) versus placebo (normal heart rate).
[001051Further, when considering peak satisfaction levels (achieved at approximately 10 minutes from the initiation of puffing (time =0) and looking at the slope of the line for plasma concentrations, the approximate slope of those cannabinoid formulations that exceeded oral cannabinoid formulations range between 3.1307 hrn/sec and 2.3442 hrn/scc. By comparison, the average slope of the line for the oral cannabinoid formulations is about 0.418. This would suggest that the concentration of available cannabinoid will be delivered to the user at a rate that is between 5.6 and 7.5 times faster than an oral formulation.

Date Recue/Date Received 2023-01-12 [00106] In another measure of performance; Cmax ¨ Maximum blood cannabinoid concentration; it is anticipated that similar rates of increase will be measured in blood cannabinoid concentration, as those illustrated above. That is, it was anticipated based on the findings herein, and unexpected based on the art known to date, that there would be comparable Cmax between the common cannabis cigarette and certain cannabinoid formulations, but with a lower Cmax in a cannabinoid solution.
[00107] Similarly, anticipated based on the findings herein, certain cannabinoid formulations would have higher rate of cannabinoid uptake levels in the blood at early time periods. Indeed, Example 8 presents data for multiple cannabinoid formulations consistent with these predictions which were made based on the findings and tests noted herein.
Example 7: Heart rate study of cannabinoid solutions via e-cigarette 100108]Exemplary formulations of cannabinoids and a control of propylene glycol are prepared as noted in Example 1 and are administered in the same fashion by an electronic cigarette to the same human subject. About 3mL of each solution is loaded into an electronic vaporization device's atomizer to be used in the study. The atomizer is then attached to an electronic vaporization device (same manufacturer). The operating temperature of the e-cigarette is from about 75 C to about 325 C, or from about 100 C to about 300 C.
[00109] Heart rate measurements arc taken for 200 minutes; from 10 minutes before start of puffing, for 10 minutes during puffing, and continuing until 190 minutes after end of puffing.
The test participant takes puffs ad libitum over 5 minutes in each case. The base heart rate is the average heart rate over the first 10 minutes before start of puffing. Heart rate after puffing started is averaged over 1 minute intervals.
Example 8: Blood Plasma testing [00110] Blood plasma testing was conducted on eleven subjects (n = 11).
Seven test articles were used in this study: one reference cannabis cigarette and six blends either administered orally, or used in a electronic vaporizing device having an operating temperature of the c-cigarette from about 75 C to about 325 C, or from about 100 C to about 300 C. The reference cannabis cigarette was obtained from the U.S. National Institute on Drug Abuse NIDA).
The blends were formulations prepared as described in Example 1.
[00111] The concentration of cannabinoid in each of the formulations was confirmed using spectroscopic analysis including UV absorbance, infrared-spectral analysis, (GC-) mass spectrometry, and spectrophotometric analysis. Cannabinoids that were available as calibrated Date Recue/Date Received 2023-01-12 certified standards were diluted to a concentration of 0.01 rrig/mL in ethanol to determine analyze molar extinction coefficients in the range of 200 to 400 nm. The control/bank measurement was obtained with ethanol. UV-spectra were recorded using a Varian Cary 1 Bio UV-Visible spectrophotometer controlled by Cary 1/3E system software, version 3.02. A
sample Cell of 1 Omm was used for all measurements. Cannabinoid concentrations reported for all formulations were within the range of 95%-105% of the claimed concentrations [00112] All subjects were able to consume about 40mg of cannabinoid in each tested blend.
[00113]Blood and plasma cannabinoid concentration results:
Low-dose formulation: Tmax = 0.17h (0.15-0.25), Cmax = 48.6 ug/L (2.3-102) High-dose formulation: Tmax = 0.17h (0.12-0.37), Cmax = 97.8 Lig/L (24.5-339) [00114] Estimated Cmax of 30% cannabinoid blends:
Cmax = Mass consumed * Strength * Bioavailability / (Vol of Distribution *
Body Weight) =
40mg * 30% * 30%! (3.4L/kg * 75kg) = 14.12 ng/mL
[00115] Estimated Cmax of 45% cannabinoid blends:
Cmax = Mass consumed * Strength * Bioavailability / (Vol of Distribution *
Body Weight) =
40mg * 45% * 30% I (3.4L/kg * 75kg) = 21.18 ng/mL
1001161Pharmacokinetic profiles of the blood plasma testing are shown in FIG.
4; showing blood cannabinoid concentrations (lga-) over time after oral administration, the first puff (inhalation) of the vaporized aerosol, or the smoke of the cannabis cigarette. Puffs were taken ad libitum starting at time =0 and continuing for 10 minutes. For ease of reference and review of FIG. 4, at the 25-minute time-point, the curves on the graph show from top to bottom (highest average blood cannabinoid concentration to lowest average blood cannabinoid concentration) arc cannabis cigarette, high-dose cannabinoid, low-dose cannabinoid, 120mg oral, 60mg oral, 30mg oral, and placebo. Although noted as highest to lowest at this time point, this is not to say that there is a statistically significant difference between any of the cannabinoid formulations, or between any of the cannabinoid formulations and the cannabis cigarette. However, it is possible there may be a statistically significant difference between the Cmax of particular cannabinoid formulations, and it is also likely based on the data shown in FIG. 4 and in other studies herein that the oral cannabinoid formulation is statistically different from cannabinoid formulations and/or the cannabis cigarette with respect to Cmax, since it appears lower than others tested at several time points. One of skill in the art, upon review of the disclosure herein could properly power a test to determine actual statistically-based differences between one or more formulations and the cigarette, or between the formulations themselves in an e-cigarette.
1001171Comparison of Tmax and Cmax of the five blends and reference cannabis cigarette are shown in Date Recue/Date Received 2023-01-12 FIG. 5. Comparison of Cmax and AUC of the five blends and reference cigarette are shown in FIG. 6. Thc data in FIGS. 4-6 show corrected blood cannabinoid concentration values (i.e.
apparent blood cannabinoid concentration at each time point minus baseline cannabinoid concentration of the same sample).
100118] Although the Tmax and Cmax values are comparable between the tested blends and the reference cannabis cigarette, the rates of cannabinoid absorption within the first 90 seconds differed among the test articles. Some blends showed markedly higher rates of absorption within the first 90 seconds compared to the other blends and with the reference cannabis cigarette. These blends contain cannabinoids which performed well in the Satisfaction Study of Example 3.
Moreover, different concentrations of cannabinoid formulations had comparable rates of absorption, suggesting that a lower concentration of cannabinoid may not adversely impact the rate of absorption.
Example 9: Blood Plasma testing 1001191 Blood plasma testing is conducted on twenty subjects (n = 20).
Five test articles are used in this study: one reference cigarette and three blends delivered to a user in an c- cigarette as an aerosol. The operating temperature of the c-cigarette is from about 75 C to about 325 C, or from about 100 C to about 300 C. The reference is a traditional cannabis cigarette.
Three blends are tested: 15%, 30%, and 45% concentrations. The three blends are liquid formulations prepared according to protocols similar to that described infra and in Example 1.
1001201 All subjects are to consume about 40 mg of the liquid formulation of each tested blend.
Puffs arc to be taken ad libitum starting at time =0 and continuing for minutes. Blood plasma testing is to occur for at least 120 minutes from the first puff (t=0) Phan-nacokinetic data (e.g., Cmax, Tmax, AUC) for cannabinoids in the plasma of users are obtained at various time periods during those 120 minutes, along with rates of cannabinoid absorption within the first 90 seconds for each test article.
Example 10: Blood Plasma testing 1001211 Blood plasma testing is conducted on twenty subjects (n = 20).
Several test articles are used in this study: one reference cannabis cigarette and several blends delivered to a user in an c-cigarette as an aerosol. The reference is a traditional cannabis cigarette.
The operating temperature of the e-cigarette is from about 75 C to about 325 C, or from about 100 C to about 300 C. Various blends and concentrations are tested: 15%, 30%, 45%, etc. The blends are Date Recue/Date Received 2023-01-12 liquid formulations prepared according to protocols similar to that described infra and in Example 1.
1001221 All subjects are to consume about 40 mg of the liquid formulation of each tested blend.
Puffs are to be taken ad libitum starting at time =0 and continuing for minutes. Blood plasma testing is to occur for at least 120 minutes from the first puff (t=0).
Pharmacokinetic data (e.g., Cmax, Tmax, AUC) for cannabinoids in the plasma of users are obtained at various time periods during those 120 minutes, along with rates of cannabinoid absorption within the first 90 seconds for each test article.
Example 11: Blood Plasma testing 1001231 Blood plasma testing is conducted on twenty subjects (n = 20). Several test articles are used in this study: one reference cannabis cigarette and several blends delivered to a user in an e-cigarette as an aerosol. The reference is a traditional cannabis cigarette.
The operating temperature of the e-cigarette is from about 75 C to about 325 C, or from about 100 C to about 300 C. Various blends and concentrations are tested:15%, 30%, 45%, etc. The blends are liquid formulations prepared according to protocols similar to that described infra and in Example I.
1001241 All subjects are to consume about 40 mg of the liquid formulation of each tested blend.
Puffs are to be taken ad libitum starting at time ¨0 and continuing for 10 minutes. Blood plasma testing is to occur for at least 120 minutes from the first puff (t=0).
Pharmacokinetic data (e.g., Cmax, Tmax, AUC) for cannabinoids in the plasma of users are obtained at various time periods during those 120 minutes, along with rates of cannabinoid absorption within the first 90 seconds for each test article.
Example 12: Blood Plasma testing 1001251 Blood plasma testing is conducted on twenty subjects (n = 20). Several test articles arc used in this study: one reference cigarette and several blends delivered to a user in an e-cigarette as an aerosol. The reference is a traditional cannabis cigarette. The operating temperature of the e-cigarette is from about 75 C to about 325 C, or from about 100 C to about 300 C. Various blends are tested: 15%, 30%, 45%, etc. The blends are liquid formulations prepared according to protocols similar to that described infra and in Example 1.
100126] All subjects arc to consume about 40 mg of the liquid formulation of each tested blend.
Puffs are to be taken ad libitum starting at time =0 and continuing for 10 minutes. Blood plasma testing is to occur for at least 120 minutes from the first puff (t=0).
Pharmacokinetic data (e.g., Cmax, Tmax, AUC) for cannabinoids in the plasma of users are obtained at various time periods during those 120 minutes, along with rates of cannabinoid absorption within the first 90 seconds Date Recue/Date Received 2023-01-12 for each test article.
=
1001271 Further understanding may be gained through contemplation of the numbered embodiments below.
1. A method of delivering cannabinoid to a user comprising operating an electronic cigarette to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
2. A method of delivering cannabinoid to a user comprising operating an electronic cigarette to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
3. A method of delivering cannabinoid to a user comprising operating an electronic cigarette wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
4. A method of delivering cannabinoid to a user comprising providing an electronic cigarette to a user wherein the electronic cigarette comprises a cannabinoid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point, and inhaling an aerosol generated from the cannabinoid formulation heated by the electronic cigarette.
5. The method of any one of embodiments 1-3, wherein an operating temperature is from 150 C to 250 C.

6. The method of any one of embodiments 1-3, wherein an operating temperature iS from 180 C to 220 C.

7. The method any one of embodiments 1-3, wherein an operating temperature is about

8. The method of embodiment 4, wherein the operating temperature is from 150 C to 220 C

9. The method of embodiment 4, wherein the operating temperature is from 180 C to Date Recue/Date Received 2023-01-12 250 C.

10. The method of embodiment 4, wherein the operating temperature is about 200 C.

11. The method any one of embodiments 1-10, wherein the aerosol comprises condensate of cannabinoid.

12. The method any one of embodiments 1-10, wherein the aerosol comprises condensate of multiple cannabinoids.

13. The method any one of embodiments 1-10, wherein the aerosol comprises condensate of cannabinoid and condensate of the carrier.

14. The method any one of embodiments 1-10, wherein the aerosol comprises condensate of cannabinoid and condensate of the organic solvent.

15. The method any one of embodiments 1-14, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 5 microns.

16. The method any one of embodiments 1-14, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 1 or 2 microns.

17. The method any one of embodiments 1-14, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 0.7 microns.

18. The method any one of embodiments 1-14, wherein the aerosol comprises condensate in particle sizes from about 0.3 microns to about 0.4 microns.

19. The method any one of embodiments 1-18, wherein the organic solvent is CO2.

20. The method of any one of embodiments 1-18, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

21. The method of embodiment 20, wherein the organic solvent is propane, butane, pentane.

22. The method of embodiment 20, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonanc, decane, undecanc, dodccane, tridecane, tetradecane, pentadecane, hexadecanc, hcptadecane, octadecanc, nonadccane, eicosane.

23. The method of any one of embodiments 1-22, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

24. The method of any one of embodiments 1-22, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

25. The method of any one of embodiments 1-22, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

26. The method of any one of embodiments 1-22, wherein the liquid carrier comprises 70%
propylene glycol and 30% vegetable glycerin.

27. The method of any one of embodiments 1-26, wherein the cannabinoid is in an amount Date Recue/Date Received 2023-01-12 that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

28. The method of any one of embodiments 1-26, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalable aerosol.

29. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

30. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

31. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

32. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20% (w/w).

33. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15% (w/w).

34. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

35. The method of any one of embodiments 1-28, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

36. The method of any one of embodiments 1-35, wherein the formulation further comprises a flavorant.

37. The method of any one of embodiments 1-36, wherein the formulation is non-corrosive to an electronic cigarette.

38. The method of any one of embodiments 1-37, wherein the organic solvent is stable at and below operating temperature or about 200 C.

39. The method of any one of embodiments 1-38, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

40. The method of any one of embodiments 1-39, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

41. The method of any one of embodiments 1-40, wherein the formulation is non-corrosive to the electronic cigarette.

42. The method of any one of embodiments 1-41, wherein the formulation is non-toxic to a user of the electronic cigarette.

43. The method of any one of embodiments 1-42, wherein the formulation further comprises one or more additional cannabinoids in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

44. The method of embodiment 43, wherein a second organic solvent used to form the Date Recue/Date Received 2023-01-12 additional cannabinoid is selected from the group consisting of CO2, propane, butane, pentane.

45. A method of delivering cannabinoid to the blood of a user, said method comprising providing an aerosol that is inhaled by the user from an electronic cigarette that comprises a cannabinoid formulation wherein providing the aerosol comprises the electronic cigarette heating the formulation thereby generating the aerosol, wherein the aerosol is effective in delivering a level of cannabinoid in the blood of the user that is at least 0.20ng/mL at about 1.5 minutes after a first puff of ten puffs of the aerosol, each puff taken at 30 second intervals.

46. The method of embodiment 42, wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C.

47. The method of embodiment 42, wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C.

48. The method of embodiment 42, wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point < 55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point.

49. The method of any one of embodiments 45-48, wherein the heating of the formulation is at a temperature from 75 C to 325 C.

50. The method of any one of embodiments 45-48, wherein the heating of the formulation is at a temperature from 180 C to 220 C.

51. The method of any one of embodiments 45-48, wherein the heating of the formulation is at a temperature of about 200 C.

52. The method of embodiment 42, wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than the operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point; and the operating temperature is 200 C.

53. The method of any one of embodiments 45-52, wherein the Cmax is over 10 ng/mL on average.

54. The method of any one of embodiments 45-52, wherein the Cmax is over 11 ng/mL on average.

55. The method of any one of embodiments 45-52, wherein the Cmax is between 10 ng/mL
and 16 ng/mL on average.
Date Recue/Date Received 2023-01-12

56. The method of any one of embodiments 45-52, wherein the Cmax is between 11 ng/mL
and 15 ng/mL on average.

57. The method of any one of embodiments 45-52, wherein the Cmax is between 11 ng/mL
and 14 ng/mL on average.

58. The method of any one of embodiments 45-57, wherein the Tmax under 25 minutes on , average.

59. The method of any one of embodiments 45-57, wherein the Tmax is under 20 minutes on average.

60. The method of any one of embodiments 45-57, wherein the Tmax is under 15 minutes on average.

61. The method of any one of embodiments 45-57, wherein the Tmax is under 10 minutes on average.

62. The method of any one of embodiments 42-51, wherein the Tmax is from 3 minutes to 15 minutes on average.

63. The method of any one of embodiments 45-57, wherein the Tmax is from 3 minutes to 7.5 minutes on average.

64. The method of any one of embodiments 45-63, wherein the aerosol comprises condensate of the cannabinoid.

65. The method of any one of embodiments 45-63, wherein the aerosol comprises condensate of cannabinoid.

66. The method of any one of embodiments 45-63, wherein the aerosol comprises condensate of cannabinoid and condensate of the carrier.

67. The method of any one of embodiments 45-63, wherein the aerosol comprises condensate of cannabinoid and condensate of the organic solvent.

68. The method of any one of embodiments 45-67, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 5 microns.

69. The method of any one of embodiments 45-67, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 1 or 2 microns.

70. The method of any one of embodiments 45-67, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 0.7 microns.

71. The method of any one of embodiments 45-67, wherein the aerosol comprises condensate in particle sizes from about 0.3 microns to about 0.4 microns.

72. The method of any one of embodiments 45-71, wherein the organic solvent is CO2.

73. The method of any one of embodiments 45-71, wherein the organic solvent used to form Date Recue/Date Received 2023-01-12 said cannabinoid is a hydrocarbon.

74. The method of embodiment 73, wherein the organic solvent is propane, butane, pentane.

75. The method of embodiment 73, wherein the organic acid is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecanc, tridecane, tetradecane, pentadecanc, hexadecane, heptadecane, octadecane, nonadecane, eicosanc.

76. The method of any one of embodiments 45-75, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

77. The method of any one of embodiments 45-75, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

78. The method of any one of embodiments 45-75, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

79. The method of any one of embodiments 45-75, wherein the liquid carrier comprises 70%
propylene glycol and 30% vegetable glycerin.

80. The method of any one of embodiments 45-79, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

81. The method of any one of embodiments 45-79, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalablc aerosol.

82. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

83. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

84. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

85. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20% (w/w).

86. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15% (w/w).

87. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

88. The method of any one of embodiments 45-81, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

89. The method of any one of embodiments 45-88, wherein the formulation further comprises a flavorant.

90. The method of any one of embodiments 45-89, wherein the formulation is non-corrosive to an electronic cigarette.

Date Recue/Date Received 2023-01-12

91. The method of any one of embodiments 45-90, wherein the organic solvent is stable at and below operating temperature or about 200 C.

92. The method of any one of embodiments 45-91, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

93. The method of any one of embodiments 45-92, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

94. The method of any one of embodiments 45-93, wherein the formulation is non-corrosive to the electronic cigarette.

95. The method of any one of embodiments 45-94, wherein the formulation is non-toxic to a user of the electronic cigarette.

96. The method of any one of embodiments 45-95, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

97. The method of embodiment 96, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of CO2, propane, butane, pentane.

98. A cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C.

99. A cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C.

100.A cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point.

101.A cannabinoid liquid formulation in an electronic cigarette for generating an inhalable aerosol upon heating in the electronic cigarette, the formulation in the cigarette comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.

102.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments Date Recue/Date Received 2023-01-12 98-100, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 75 C to 325 C.

103.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-100, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 180 C to 220 C.

104.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-100, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature of about 200 C.

105. The cannabinoid liquid formulation in the electronic cigarette of embodiment 101, wherein the operating temperature is from 75 C to 325 C.

106.The cannabinoid liquid formulation in the electronic cigarette of embodiment 101, wherein the operating temperature is from 180 C to 220 C.

107.The cannabinoid liquid formulation in the electronic cigarette of embodiment 101, wherein the operating temperature is about 200 C.

108.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-107, wherein the organic solvent is CO2.

109.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-107, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

110.The cannabinoid liquid formulation in the electronic cigarette of embodiment 109, wherein the organic solvent is propane, butane, pentane.

111.The cannabinoid liquid formulation in the electronic cigarette of embodiment 109, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decanc, undccanc, dodccane, tridecane, tetradecane, pentadecane, hexadecane, heptadecanc, octadecane, nonadecane, eicosane.

112.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-111, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylenc glycol, water, ethanol or combinations thereof.

113. The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-111, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

114.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-111, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

115.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 122-147, wherein the liquid carrier comprises 70% propylene glycol and 30%
vegetable glycerin.

116. Thc cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-Date Recue/Date Received 2023-01-12 111, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

117.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-115, wherein the cannabinoid is in an amount that forms about 1% to about 50%
cannabinoid in the inhalable aerosol.

118.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-115, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50%
(w/w).

119.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-117, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45%
(w/w).

120.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-117, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30%
(w/w).

121.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-117, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20%
(w/w).

122.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-117, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15%
(w/w).

123.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-117, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

124.Thc cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-117, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

125.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-124, wherein the formulation further comprises a flavorant.

126.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-125, wherein the formulation is non-corrosive to an electronic cigarette.

127.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-126, wherein the organic solvent is stable at and below operating temperature or about 200 C.

128.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-127, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

129.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-128, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

130.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-Date Recue/Date Received 2023-01-12 129, wherein the formulation is non-corrosive to the electronic cigarette.

131.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-130, wherein the formulation is non-toxic to a user of the electronic cigarette.

132.The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments 98-131 further comprising one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

133.The cannabinoid liquid formulation in the electronic cigarette of embodiment 132, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of alkanes.

134.A cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C.

135.A cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C.

136.A cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point.

137.A cannabinoid liquid formulation for generating an inhalable aerosol upon heating in the electronic cigarette, the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.

138. The cannabinoid liquid formulation of any one of embodiments 134-136, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 75 C to 325 C.

139. The cannabinoid liquid formulation of any one of embodiments 134-136, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 180 C to 220 C.

140. The cannabinoid liquid formulation of any one of embodiments 134-136, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature of about 200 C.

Date Recue/Date Received 2023-01-12

141. The cannabinoid liquid formulation of embodiment 137, wherein the operating temperature is from 75 C to 325 C.

142. The cannabinoid liquid formulation of embodiment 137, wherein the operating temperature is from 180 C to 220 C.

143. The cannabinoid liquid formulation of embodiment 137, wherein the operating temperature is about 200 C.

144. The cannabinoid liquid formulation of any one of embodiments 134-143, wherein the organic solvent is CO2.

145. The cannabinoid liquid formulation of any one of embodiments 134-143, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

146. The cannabinoid liquid formulation of embodiment 145, wherein the organic solvent is propane, butane, pentane.

147. The cannabinoid liquid formulation of embodiment 145, wherein the organic solvent is = CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decanc, undecane, dodecane, tridecane, tetradecane, pentadccane, hexadecane, heptadecane, octadecane, nonadecane, eicosane.

148. The cannabinoid liquid formulation of any one of embodiments 134-147, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof

149. The cannabinoid liquid formulation in the electronic cigarette of any one of embodiments ' 134-147, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

150. The cannabinoid liquid formulation of any one of embodiments 134-147, wherein the liquid carrier comprises propylene glycol and vegetable glycerin liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

151. The cannabinoid liquid formulation of any one of embodiments 134-147, wherein the liquid carrier comprises 70% propylene glycol and 30% vegetable glycerin.

152. The cannabinoid liquid formulation of any one of embodiments 134-151, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

153 The cannabinoid liquid formulation of any one of embodiments 134-151, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalable aerosol.

154 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50%
(w/w).

155 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45%
(w/w).

156 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about I% (w/w) to about 30%
(w/w).

Date Recue/Date Received 2023-01-12

157 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20%
(w/w).

158 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15%
(w/w).

159 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

160 The cannabinoid liquid formulation of any one of embodiments 134-153, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

161 The cannabinoid liquid formulation of any one of embodiments 134-160, wherein the formulation further comprises a flavorant.

162 The cannabinoid liquid formulation of any one of embodiments 134-161, wherein the formulation is non-corrosive to an electronic cigarette.

163 The cannabinoid liquid formulation of any one of embodiments 134-162, wherein the organic solvent is stable at and below operating temperature or about 200 C.

164 The cannabinoid liquid formulation of any one of embodiments 134-163, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

165 The cannabinoid liquid formulation of any one of embodiments 134-164, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

166 The cannabinoid liquid formulation of any one of embodiments 134-165, wherein the formulation is non-corrosive to the electronic cigarette.

167 The cannabinoid liquid formulation of any one of embodiments 134-166, wherein the formulation is non-toxic to a user of the electronic cigarette.

168 The cannabinoid liquid formulation of any one of embodiments 134-167, further comprising one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

169 The cannabinoid liquid formulation of embodiment 168, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of the alkanes. .

170 A cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C.

171 A cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C.

172 A cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid Date Recue/Date Received 2023-01-12 formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point.

173 A cannabinoid liquid formulation for use in an electronic cigarette the cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15- degree difference between the melting point and the boiling point.

174 The cannabinoid liquid formulation of any one of embodiments 170-172, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 75 C to 325 C.

175 The cannabinoid liquid formulation of any one of embodiments 170-172, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 180 C to 220 C.

176 The cannabinoid liquid formulation of any one of embodiments 170-172, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature of about 200 C.

177 The cannabinoid liquid formulation of embodiment 173, wherein the operating temperature is from 75 C to 325 C.

178 The cannabinoid liquid formulation of embodiment 173, wherein the operating temperature is from 180 C to 220 C.

179 The cannabinoid liquid formulation of embodiment 173, wherein the operating temperature is about 200 C.

180 The cannabinoid liquid formulation of any one of embodiments 170-179, wherein the organic solvent is CO2.

181 The cannabinoid liquid formulation of any one of embodiments 170-179, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

182 The cannabinoid liquid formulation of embodiment 181, wherein the organic solvent is propane, butane, pentane.

183 The cannabinoid liquid formulation of embodiment 181, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptanc, octane, nonanc, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadccane, nonadecane, eicosane.

184 The cannabinoid liquid formulation of any one of embodiments 170-183, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

Date Recue/Date Received 2023-01-12

185 The cannabinoid liquid formulation of any one of embodiments 170-183, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

186 The cannabinoid liquid formulation of any one of embodiments 170-183, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

187 The cannabinoid liquid formulation of any one of embodiments 170-183, wherein the liquid carrier comprises 70% propylene glycol and 30% vegetable glycerin.

188 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

189 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalable aerosol.

190 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50%
(w/w).

191 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45%
(w/w).

192 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30%
(w/w).

193 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20%
(w/w).

194 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15%
(w/w).

195 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

196 The cannabinoid liquid formulation of any one of embodiments 170-187, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

197 The cannabinoid liquid formulation of any one of embodiments 170-196, wherein the formulation further comprises a flavorant.

198 The cannabinoid liquid formulation of any one of embodiments 170-197, wherein the formulation is non-corrosive to an electronic cigarette.

199 The cannabinoid liquid formulation of any one of embodiments 170-198, wherein the organic solvent is stable at and below operating temperature or about 200 C.

200 The cannabinoid liquid formulation of any one of embodiments 170-199, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

201 The cannabinoid liquid formulation of any one of embodiments 170-200, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

202 The cannabinoid liquid formulation of any one of embodiments 170-201, wherein the Date Recue/Date Received 2023-01-12 formulation is non-corrosive to the electronic cigarette.

203 The cannabinoid liquid formulation of any one of embodiments 170-202, wherein the formulation is non-toxic to a user of the electronic cigarette.

204 The cannabinoid liquid formulation of any one of embodiments 170-203, further comprising one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

205 The cannabinoid liquid formulation of embodiment 204, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of alkanes.

206 Use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.

207 Use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.

208 Use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.

209 Use of a cannabinoid formulation for delivery of cannabinoid to the blood of a user from an electronic cigarette, wherein the cannabinoid formulation in the electronic cigarette is heated to form an aerosol which delivers a level of cannabinoid in the blood of the user that is at least 2 ng/mL at about 1.5 minutes after a first puff of ten puffs of the aerosol, each puff taken at 30 second intervals.

210 Use of a cannabinoid formulation for delivery of cannabinoid to a user from an electronic cigarette wherein the cannabinoid formulation comprises a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point, and the cannabinoid formulation is heated by the electronic cigarette to generate an aerosol inhalable by the user.

Date Recue/Date Received 2023-01-12

211 The use of any one of embodiments 206-209, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature is from 75 C to 315 C.

212 The use of any one of embodiments 206-209, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature is from 180 C to 220 C.

213 The use of any one of embodiments 206-209, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature is about 200 C.

214 The use of embodiment 210, wherein the operating temperature is from 75 C
to 325 C.

215 The use of embodiment 210, wherein the operating temperature is from 180 C to 220 C.

216. The use of embodiment 210, wherein the operating temperature is about 200 C.=

217. The use of any one of embodiments 206-216, wherein the aerosol comprises condensate of the cannabinoid.

218. The use of any one of embodiments 206-216, wherein the aerosol comprises condensate of freebase cannabinoid.

219. The use of any one of embodiments 206-216, wherein the aerosol comprises condensate of freebase cannabinoid and condensate of the carrier.

220. The use of any one of embodiments 206-216, wherein the aerosol comprises condensate of freebase cannabinoid and condensate of the organic solvent.

221. The use of any one of embodiments 206-220, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 5 microns.

222. The use of any one of embodiments 206-220, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 1 or 2 microns.

223. The use of any one of embodiments 206-220, wherein the aerosol comprises .
condensate in particle sizes from about 0.1 microns to about 0.7 microns.

224. The use of any one of embodiments 206-220, wherein the aerosol comprises condensate in particle sizes from about 0.3 microns to about 0.4 microns.

225. The use of any one of embodiments 206-224, wherein the organic solvent is CO2.

226. The use of any one of embodiments 206-224, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

227. The use of embodiment 226, wherein the organic solvent is propane, butane, pentane.

228. The use of embodiment 226, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, &cane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane, eicosane.

229. The use of any one of embodiments 206-228, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

Date Recue/Date Received 2023-01-12

230. The use of any one of embodiments 206-228, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

231. The use of any one of embodiments 206-228, wherein the liquid carrier comprises 80% to .
50% of propylene glycol and 20% to 50% of vegetable glycerin.

232. The use of any one of embodiments 206-228, wherein the liquid carrier comprises 70%
propylene glycol and 30% vegetable glycerin.

233. The use of any one of embodiments 206-232, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

234. The use of any one of embodiments 206-232, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalable aerosol.

235. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

236. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

237. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

238. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20% (w/w).

239. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15% (w/w).

240. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

241. The use of any one of embodiments 206-234, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

242, The use of any one of embodiments 206-241, wherein the formulation further comprises a flavorant.

243. The use of any one of embodiments 206-242, wherein the formulation is non-corrosive to an electronic cigarette.

244. The use of any one of embodiments 206-243, wherein the organic solvent is stable at and below operating temperature or about 200 C.

245. The use of any one of embodiments 206-244, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

246. The use of any one of embodiments 206-245, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

247. The use of any one of embodiments 206-246, wherein the formulation is non-Date Recue/Date Received 2023-01-12 corrosive to the electronic cigarette.

248. The use of any one of embodiments 206-247, wherein the formulation is non-toxic to a user of the electronic cigarette.

249. The use of any one of embodiments 206-248, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

250. The use of embodiment 249, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of alkanes.

251. A cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.

252. A cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.

253. A cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.

254.A cartomizer for an electronic cigarette comprising:
a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid Date Recue/Date Received 2023-01-12 carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point;
an atomizer comprising a heating element in fluid communication with the cannabinoid liquid formulation; and a fluid storage compartment that stores the cannabinoid liquid formulation.

255. The cartomizer of any one of embodiments 251-253, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 75 C to 325 C.

256. The cartomizer of any one of embodiments 251-253, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 180 C to 220 C.

257. The cartomizer of any one of embodiments 251-253, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature of about 200 C.

258. The cartomizer of embodiment 254, wherein the operating temperature is from 75 C to 325 C.

259. The cartomizer of embodiment 254, wherein the operating temperature is from 180 C to 220 C.

260. The cartomizer of embodiment 254, wherein the operating temperature is about 200 C.

261. The cartomizer of any one of embodiments 251-260, wherein the cartomizer further comprises a mouthpiece.

262. The cartomizer of any one of embodiments 251-261, wherein the organic solvent is CO2.

263. The cartomizer of any one of embodiments 251-261, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

264. The cartomizer of embodiment 263, wherein the organic solvent is propane, butane, pentane.

265. The cartomizer of embodiment 263, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, hcptane, octane, nonane, decanc, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane, eicosane.

266. The cartomizer of any one of embodiments 251-265, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

267. The cartomizer of any one of embodiments 251-265, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

268. The cartomizer of any one of embodiments 251-265, wherein the liquid carrier Date Recue/Date Received 2023-01-12 =
comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

269. The cartomizer of any one of embodiments 251-265, wherein the liquid carrier comprises 70% propylene glycol and 30% vegetable glycerin.

270. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

271. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

272. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

273. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

274. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 20% (w/w).

275. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

276. The cartomizer of any one of embodiments 251-269, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

277. The cartomizer of any one of embodiments 251-276, wherein the electronic cigarette is configured to generate an aerosol inhalable by a user.

278. The cartomizer of embodiment 277, wherein the aerosol comprises condensate of the cannabinoid.

279. The cartomizer of embodiment 277, wherein the aerosol comprises condensate of multiple cannabinoid.

280. The cartomizer of embodiment 277, wherein the aerosol comprises condensate of cannabinoid and condensate of the carrier.

281. The cartomizer of embodiment 277, wherein the aerosol comprises condensate of cannabinoid and condensate of the organic solvent.

282. The cartomizer of any one of embodiments 277-281, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 5 microns.

283. The cartomizcr of any one of embodiments 277-281, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 1 or 2 microns.

284. The cartomizer of any one of embodiments 277-281, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 0.7 microns.

285. The cartomizer of any one of embodiments 277-281, wherein the aerosol comprises condensate in particle sizes from about 0.3 microns to about 0.4 microns.

Date Recue/Date Received 2023-01-12

286. The cartomizer of any one of embodiments 277-285, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol. =

287. The cartomizer of any one of embodiments 277-285, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalable aerosol.

288. The cartomizer of any one of embodiments 251-287, wherein the formulation further comprises a flavorant.

289. The cartomizer of any one of embodiments 251-288, wherein the formulation is non-corrosive to an electronic cigarette.

290. The cartomizer of any one of embodiments 251-289, wherein the organic solvent is stable at and below operating temperature or about 200 C.

291. The cartomizer of any one of embodiments 251-290, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

292. The cartomizer of any one of embodiments 251-291, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

293. The cartomizer of any one of embodiments 251-292, wherein the formulation is non-corrosive to the electronic cigarette.

294. The cartomizer of any one of embodiments 251-293, wherein the formulation is non- toxic to a user of the electronic cigarette.

295. The cartomizer of any one of embodiments 251-294, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

296. The cartomizer of embodiment 295, wherein a second organic solvent used to form the additional cannabinoid is selected from thc group consisting of alkanes or CO2.

297. An electronic cigarette for generating an inhalable aerosol comprising: a fluid storage compartment;
a heater; and a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure < 25 bar at 50 C;
a battery; and a mouthpiece.

298. An electronic cigarette for generating an inhalable aerosol comprising: a fluid storage compartment;
a heater; and Date Recue/Date Received 2023-01-12 a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C;
a battery; and a mouthpiece.

299. An electronic cigarette for generating an inhalable aerosol comprising: a fluid storage compartment;
a heater; and a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point; a battery; and a mouthpiece.

300. An electronic cigarette for generating an inhalable aerosol comprising: a fluid storage compartment;
a heater; and a cannabinoid liquid formulation in the fluid storage compartment, the liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point;
a battery; and a mouthpiece.

301. The electronic cigarette of any one of embodiments 297-300, wherein the heater comprises a heater chamber, a fluid wick, and a resistive heating clement in contact with the fluid wick.

302. The electronic cigarette of any one of embodiments 297-300, wherein the mouthpiece, the heater and the fluid storage compartment form a cartomizer separable from the battery.

303. The electronic cigarette of any one of embodiments 297-300, wherein the heater and the fluid storage compartment form a cartomizer separable from the battery and the mouthpiece.

304. The electronic cigarette of any one of embodiments 297-300, wherein the fluid storage compartment is separable from the heater, the battery and the mouthpiece.

305. The electronic cigarette of any one of embodiments 297-299, wherein the electronic cigarette Date Recue/Date Received 2023-01-12 heats the cannabinoid formulation to an operating temperature from 75 C to 325 C.

306. The electronic cigarette of any one of embodiments 297-299, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature from 180 C to 220 C.

307. The electronic cigarette of any one of embodiments 297-299, wherein the electronic cigarette heats the cannabinoid formulation to an operating temperature of about 200 C.

308. The electronic cigarette of embodiment 300, wherein the operating temperature is from 75 C to 325 C.

309. The electronic cigarette of embodiment 300, wherein the operating temperature is from 180 C to 220 C.

310. The electronic cigarette of embodiment 300, wherein the operating temperature is about 200 C.

311. The electronic cigarette of any one of embodiments 297-310, wherein the aerosol comprises condensate of the cannabinoid.

312. The electronic cigarette of any one of embodiments 297-310, wherein the aerosol comprises condensate of multiple cannabinoids.

313. The electronic cigarette of any one of embodiments 297-310, wherein the aerosol comprises condensate of cannabinoid and condensate of the carrier.

314. The electronic cigarette of any one of embodiments 297-310, wherein the aerosol comprises condensate of cannabinoid and condensate of the organic solvent.

315. The electronic cigarette of any one of embodiments 297-314, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 5 microns.

316. The electronic cigarette of any one of embodiments 297-314, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 1 or 2 microns.

317. The electronic cigarette of any one of embodiments 297-314, wherein the aerosol comprises condensate in particle sizes from about 0.1 microns to about 0.7 microns.

318. The electronic cigarette of any one of embodiments 297-314, wherein the aerosol comprises condensate in particle sizes from about 0.3 microns to about 0.4 microns.

319. The electronic cigarette of any one of embodiments 297-318, wherein the organic solvent is CO2.

320. The electronic cigarette of any one of embodiments 297-318, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

321. The electronic cigarette of embodiment 320, wherein the organic solvent is propane, butane, pentane.

322. The electronic cigarette of embodiment 320, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, tridecane, Date Recue/Date Received 2023-01-12 tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane, eicosane.

323. The electronic cigarette of any one of embodiments 297-323, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof

324. The electronic cigarette of any one of embodiments 297-323, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

325. The electronic cigarette of any one of embodiments 297-323, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

326. The electronic cigarette of any one of embodiments 297-323, wherein the liquid carrier comprises 70% propylene glycol and 30% vegetable glycerin.

327. The electronic cigarette of any one of embodiments 297-326, wherein the cannabinoid is in an amount that forms about 0.5% to about 50% cannabinoid in the inhalable aerosol.

328. The electronic cigarette of any one of embodiments 297-326, wherein the cannabinoid is in an amount that forms about 1% to about 50% cannabinoid in the inhalable aerosol.

329. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50%
(w/w).

330. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45%
(w/w).

331. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30%
(w/w).

332. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 20%
(w/w).

333. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 15%
(w/w).

334. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

335. The electronic cigarette of any one of embodiments 297-328, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

336. The electronic cigarette of any one of embodiments 297-335, wherein the formulation further comprises a flavorant.

337. The electronic cigarette of any one of embodiments 297-336, wherein the formulation is non-corrosive to an electronic cigarette.

338. The electronic cigarette of any one of embodiments 297-338, wherein the organic solvent is stable at and below operating temperature or about 200 C.

339. The electronic cigarette of any one of embodiments 297-339, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.
Date Recue/Date Received 2023-01-12

340. The electronic cigarette of any one of embodiments 297-340, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

341. The electronic cigarette of any one of embodiments 297-341, wherein the formulation is non-corrosive to the electronic cigarette.

342. The electronic cigarette of any one of embodiments 297-342, wherein the formulation is non-toxic to a user of the electronic cigarette.

343. The electronic cigarette of any one of embodiments 297-343, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalablc aerosol upon heating.

344. The electronic cigarette of embodiment 343, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of an alkane.

345. A cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C.

346. A cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C.

347. A cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point < 55 C, a boiling point > -165 C, and at least a 15-degree difference between the melting point and the boiling point.

348. A cartridge in an electronic cigarette comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.

349. The cartridge of any one of embodiments 345-348, wherein the cartridge is separable from the electronic cigarette.

350. The cartridge of any one of embodiments 345-349, wherein the organic solvent is CO2 Date Recue/Date Received 2023-01-12

351. The cartridge of any one of embodiments 345-349, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

352. The cartridge of embodiment 351, wherein the organic solvent is propane, butane, pentane.

353. The cartridge of embodiment 351, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane, undccane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane, eicosane.

354. The cartridge of any one of embodiments 345-353, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

355. The cartridge of any one of embodiments 345-353, wherein the liquid carrier comprises propylene glycol and vegetable glycerin,

356. The cartridge of any one of embodiments 345-353, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 80% to 50% of vegetable glycerin.

357. The cartridge of any one of embodiments 345-353, wherein the liquid carrier comprises 70% propylene glycol and 30% vegetable glycerin.

358. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

359. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

360. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

361. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

362. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 20% (w/w).

363. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

364. The cartridge of any one of embodiments 345-357, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

365. The cartridge of any one of embodiments 345-364, wherein the formulation further comprises a flavorant.

366. The cartridge of any one of embodiments 345-365, wherein the formulation is non-corrosive to an electronic cigarette.

367. The cartridge of any one of embodiments 345-366, wherein the organic solvent is stable at and below operating temperature or about 200 C.

Date Recue/Date Received 2023-01-12

368. The cartridge of any one of embodiments 345-367, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

369. The cartridge of anyone of embodiments 345-368, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

370. The cartridge of any one of embodiments 345-369, wherein the formulation is non-corrosive to the electronic cigarette.

371. The cartridge of any one of embodiments 345-370, wherein the formulation is non- toxic to a user of the electronic cigarette.

372. The cartridge of any one of embodiments 345-371, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

373. The cartridge of embodiment 372, wherein a second organic solvent used to form the = additional cannabinoid is selected from the group consisting of alkanes.

374. .. A kit comprising:
(a) an electronic cigarette for generating an inhal able aerosol comprising 1. a device body comprising a cartridge receptacle;
II a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <25 bar at 50 C;
a heater;
IV. a battery; and v. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.

375. A kit comprising:
(a) art electronic cigarette for generating an inhalable aerosol comprising I. a device body comprising a cartridge receptacle;
II a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure of about 100 to 10000 bar at 25 C;

Date Recue/Date Received 2023-01-12 ill. a heater;
IV. a battery; and v. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.

376. A kit comprising:
(a) an electronic cigarette for generating an inhalable aerosol comprising 1. a device body comprising a cartridge receptacle;
ii. a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point;
1, a heater;
IV. a battery; and v. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.

377. A kit comprising:
(a) an electronic cigarette for generating an inhalable aerosol comprising 1. a device body comprising a cartridge receptacle;
11 a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point;
i. a heater;
IV. a battery; and Date Recue/Date Received 2023-01-12 v. a mouthpiece; and (b) instructions for using the electronic cigarette to generate an inhalable aerosol.

378. The kit of any one of embodiments 374-377, wherein the organic solvent is CO2.

379. The kit of any one of embodiments 374-377, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

380. The kit of embodiment 379, wherein the organic solvent is propane, butane, pentane.

381. The kit of embodiment 379, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecanc, tridecane, tetradecane, pcntadecane, hexadecane, heptadecane, octadecane, nonadecane, eicosane.

382. The kit of any one of embodiments 374-381, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof

383. The kit of any one of embodiments 374-381, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

384. The kit of any one of embodiments 374-381, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

385. The kit of any one of embodiments 374-381, wherein the liquid carrier comprises 70%
propylene glycol and 30% vegetable glycerin.

386. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

387. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

388. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

389. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

390. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 20% (w/w).

391. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

392. The kit of any one of embodiments 374-385, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/w).

393. The kit of any one of embodiments 374-392, wherein the formulation further comprises a flavorant.

394. The kit of any one of embodiments 374-393, wherein the formulation is non-Date Recue/Date Received 2023-01-12 corrosive to an electronic cigarette.

395. The kit of any one of embodiments 374-394, wherein the organic solvent is stable at and below operating temperature or about 200 C.

396. The kit of any one of embodiments 374-395, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

397. The kit of any one of embodiments 374-396, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

398. The kit of any one of embodiments 374-397, wherein the formulation is non-corrosive to the electronic cigarette.

399. The kit of any one of embodiments 374-398, wherein the formulation is non-toxic to a user of the electronic cigarette.

400. The kit of any one of embodiments 374-399, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalablc aerosol upon heating.

401. The kit of embodiment 400, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of alkancs.

402.A cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores ,a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids are characterized by vapor pressure <
25 bar at 50 C.

403. A cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoids arc characterized by vapor pressure of about 100 to 10000 bar at 25 C.

404.A cartridge comprising a fluid storage compartment, wherein the fluid storage compai tment stores a cannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point <55 C, a boiling point> -165 C, and at least a 15-degree difference between the melting point and the boiling point.

405.A cartridge comprising a fluid storage compartment, wherein the fluid storage compat tment stores a eannabinoid liquid formulation comprising a cannabinoid in a biologically acceptable liquid carrier wherein an organic solvent used to form said cannabinoid is further characterized by a melting point at least 20 degrees lower than an operating temperature of the electronic cigarette, a boiling point no more than 300 degrees lower than the operating temperature of the electronic cigarette, and at least a 15-degree difference between the melting point and the boiling point.

Date Recue/Date Received 2023-01-12

406. The cartridge of any one of embodiments 403-406, wherein the cartridge can be connected to an electronic cigarette.

407. The cartridge of any one of embodiments 403-407, wherein the organic solvent is CO2.

408. The cartridge of any one of embodiments 403-407, wherein the organic solvent used to form said cannabinoid is a hydrocarbon.

409. The cartridge of embodiment 409, wherein the organic solvent is propane, butane, pentane.

410. The cartridge of embodiment 409, wherein the organic solvent is CO2, methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonanc, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadccanc, octadccane, nonadccane, eicosane.

411. The cartridge of any one of embodiments 403-410, wherein the liquid carrier comprises glycerol, propylene glycol, trimethylene glycol, water, ethanol or combinations thereof.

412. The cartridge of any one of embodiments 403-410, wherein the liquid carrier comprises propylene glycol and vegetable glycerin.

413. The cartridge of any one of embodiments 403-410, wherein the liquid carrier comprises 80% to 50% of propylene glycol and 20% to 50% of vegetable glycerin.

414. The cartridge of any one of embodiments 403-410, wherein the liquid carrier comprises 70% propylene glycol and 30% vegetable glycerin.

415. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

416. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 50% (w/w).

417. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 45% (w/w).

418. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 1% (w/w) to about 30% (w/w).

419. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 4% (w/w) to about 20% (w/w).

420. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 10% (w/w).

421. The cartridge of any one of embodiments 403-414, wherein the liquid formulation has a cannabinoid concentration of about 5% (w/vv).

422. The cartridge of any one of embodiments 403-421, wherein the formulation further comprises a flavorant.

423. The cartridge of any one of embodiments 403-422, wherein the formulation is non-Date Recue/Date Received 2023-01-12 corrosive to an electronic cigarette.

424. The cartridge of any one of embodiments 403-423, wherein the organic solvent is stable at and below operating temperature or about 200 C.

425. The cartridge of any one of embodiments 403-424, wherein the organic solvent does not decompose at and below operating temperature or about 200 C.

426. The cartridge of any one of embodiments 403-425, wherein the organic solvent does not oxidize at and below operating temperature or about 200 C.

427. The cartridge of any one of embodiments 403-426, wherein the formulation is non-corrosive to the electronic cigarette. =

428. The cartridge of any one of embodiments 403-427, wherein the formulation is non- toxic to a user of the electronic cigarette.

429. The cartridge of any one of embodiments 403-428, wherein the formulation further comprises one or more additional cannabinoid in a biologically acceptable liquid carrier suitable for generating the inhalable aerosol upon heating.

430. The cartridge of embodiment 429, wherein a second organic solvent used to form the additional cannabinoid is selected from the group consisting of alkanes.
1001281 Although preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein can be employed in practicing the invention. It is intended that the following embodiments define the scope of the invention and that methods and structures within the scope of these embodiments and their equivalents be covered thereby.

Date Recue/Date Received 2023-01-12

Claims

1. A cannabinoid formulation comprising:
(i) a cannabinoid extract, wherein said cannabinoid extract is formed using a suitable organic solvent selected from the group consisting of methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane, and eicosane;
and (ii) a biologically acceptable liquid carrier comprising about 10% - about 70%
(w/w) propylene glycol and about 90% - about 30% (w/w) vegetable glycerin;
wherein the stoichiometric ratio of the cannabinoid to solvent is from about 1:5 to about 5:64.

2. A cannabinoid formulation comprising:
(i) at least one synthetic cannabinoid;
(ii) a solvent, wherein the solvent comprises a suitable organic solvent selected from the group consisting of methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane, and eicosane; and (iii) a biologically acceptable liquid carrier comprising about 10% - about 70% (w/w) propylene glycol and about 90% - about 30% (w/w) vegetable glycerin;
wherein the stoichiometric ratio of the cannabinoid to solvent is from about 1:5 to about 5:64.

3. The formulation of claim 1, further comprising at least one synthetic cannabinoid.

4. The formulation of any one of claims 2-3, wherein the synthetic cannabinoid has a purity of greater than about 80% pure, greater than about 85% pure, greater than about 90% pure, greater than about 95% pure, or greater than about 99 % pure.

5. The formulation of any one of claims 1-4 wherein the liquid carrier comprises about 70% (w/w) to about 50% (w/w) of propylene glycol and about 30% (w/w) to about 50% (w/w) of vegetable glycerin.

6. The formulation of any one of claims 1-5, wherein the organic solvent is propane, butane, or pentane.

7. The formulation of any one of claims 1-6, wherein the liquid carrier further comprises glycerol, trimethylene glycol, water, ethanol, or combinations thereof.

8. The formulation of any one of claims 1-7, further comprising one or more flavourants.

9. The formulation of any one of claims 1-8, wherein the stoichiometric ratio of the cannabinoid to organic solvent is about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:11, about 1:12, about 1:13, about 2:21, about 2:23, about 2:25, about 3:31, about 3:32, about 3:34, about 3:35, about 3:37, about 3:38, about 4:41, about 4:42, about 4:43, about 4:45, Date Regue/Date Received 2023-01-12 about 4:46, about 4:47, about 4:49, about 4:50, about 5:51, about 5:52, about 5:53, about 5:54, about 5:56, about 5:57, about 5:58, about 5:59, about 5:61, about 5:62, about 5:63, or about 5:64.

10. An electronic cigarette for delivering an inhalable aerosol comprising:
(a) a fluid storage compartment, (b) the cannabinoid liquid formulation of any one of claims 1-9 disposed within the fluid storage compartment, (c) an atomizer comprising a heating element, (d) a battery, and (e) a mouthpiece.

11. The electronic cigarette of claim 10, wherein the heating element has an operating temperature of about 200 C.

12. A cartomizer for an electronic cigarette, the cartomizer comprising the formulation of any one of claims 1-9, a fluid storage compaitinent, and an atomizer comprising a heating element in fluid communication with the formulation.

13. A cathidge for use in an electronic cigarette, the cartridge comprising a fluid storage compartment comprising the formulation of any one of claims 1-9.

14. A kit comprising:
a) an electronic cigarette for generating an inhalable aerosol comprising:
i. a device body comprising a cathidge receptacle, ii. a cartridge comprising a fluid storage compartment, wherein the fluid storage compartment stores the formulation of any one of claims 1-9, iii. a heater, iv. a battery, and v. a mouthpiece; and b) instructions for using the electronic cigarette to generate an inhalable aerosol.

15. Use of a cannabinoid formulation for delivery of cannabinoid to a user, , comprising, providing to the user the formulation of any one of claims 1-9, wherein the formulation can be heated to generate an inhalable aerosol comprising one or more cannabinoids, and one or more of the cannabinoids are inhaled by the user in the inhalable aerosol.

16. The use of the cannabinoid formulation of claim 15, wherein the formulation is aerosolized with the electronic cigarette of claim 10.

17. The use of the cannabinoid formulation of any one of claims 15-16, wherein the formulation is heated with the electronic cigarette operated at about 200 C.

18. The use of the cannabinoid formulation of any one of claims 15-17, wherein inhaling the aerosol Date Regue/Date Received 2023-01-12 results in a maximum blood cannabinoid concentration (Cmax) of over 10 ng/ml.

19. The use of the cannabinoid formulation of any one of claims 15-18, wherein inhaling the aerosol results in a time at which the maximum concentration of cannabinoid is measured (T..) at under 25 minutes, under 20 minutes, under 15 minutes, or under 10 minutes.

20. The formulation of any one of claims 2-19, wherein the one or more synthetic cannabinoids have a purity of greater than about 80% pure, greater than about 85% pure, greater than about 90% pure, greater than about 95% pure, or greater than about 99 % pure.

Date Regue/Date Received 2023-01-12