http://pubs.acs.org/doi/full/10.1021/acsomega.7b01130
Abstract
Inhalable, noncombustible cannabis products are playing a central role in the expansion of the medical and recreational use of cannabis. In particular, the practice of “dabbing” with butane hash oil has emerged with great popularity in states that have legalized cannabis. Despite their growing popularity, the degradation product profiles of these new products have not been extensively investigated. The study herein focuses on the chemistry of myrcene and other common terpenes found in cannabis extracts. Methacrolein, benzene, and several other products of concern to human health were formed under the conditions that simulated real-world dabbing. The terpene degradation products observed are consistent with those reported in the atmospheric chemistry literature.
Topics:
Extraction; Organic compounds and Functional groups; Solvation; Toxicology
Introduction
Terpenes and terpenoids are present in such a wide diversity of environments (nature, food, cosmetics, pharmaceuticals, and drugs) that their consequences for inhalation toxicology cannot be ignored. Additionally, their inclusion in flavored electronic cigarettes(1) and ubiquitous presence in inhalable cannabis products are of particular concern. The medicinal and psychoactive effects of cannabis have been proposed to be enhanced by terpenes, a phenomenon known as the “entourage effect”,(2) and these relatively unsubstantiated assertions of benefits have led the cannabis industry to place a heavy emphasis on these aroma compounds.
Terpenoid degradation in the context of cannabis has not been extensively studied;(3, 4) however, it has attracted attention in the context of atmospheric chemistry.(5, 6) For instance, the reactions of terpenoids with O3 and NOx are well-known, but they are not directly applicable to e-cigarettes or inhalable cannabis products. However, these and other studies of pyrolysis and combustion of terpenoids should serve as a starting point toward understanding the reaction pathways in consumer vaporization devices. Despite the growing popularity of flavored e-cigarettes and terpene-enriched cannabis extracts, the chemical profiles of their terpene degradation products have not been evaluated in detail.
Of very recent concern is the practice of dabbing, which has emerged as a dangerous and rapidly growing trend in cannabis consumption. It consists of inhaling the vapors produced by placing a small amount of cannabis extract (a “dab”) on a small heated surface (the “nail”), which is connected to a water pipe.(7) Its delivery of harmfully large amounts cannabinoids(8, 9) represents a potential danger to consumers, but little is known about the toxicants the process may produce.
The principal extract used in dabbing is butane hash oil (BHO). BHO is a resinous, nonpolar extract of the cannabis made using butane as a solvent.(10) BHO has active ingredient (tetrahydrocannabinol (THC) or cannabidiol) contents ranging between 50 and 90%,(8, 11) with terpene content ranging from 0.1 to 34% (unpublished). Myrcene is unequivocally the most abundant terpene in cannabis, followed by limonene, linalool, pinene, caryophyllene, and humulene; however, the plant can contain up to 68 additional terpenic compounds in trace amounts.(12) Additionally, some consumers increase the terpenoid content by dipping BHO in a vial of terpenes prior to use (“terp dipping”).(13)
BHO is made by passing butane over cannabis buds and leaves, and subsequently “purging” the butane from the product under vacuum at room temperature or in an oven. Different nuances in its processing can lead to slightly different consistencies, which take on terms such as shatter, budder, crumble, pull-and-snap, wax, and so on. In all of its forms, the extract is a sticky, resinous substance similar to the oleo-resins of other plants.(14) Because the process does not involve heating the extract to the point that delta-9-tetrahydrocannabinolic acid (THCA, the native form of this substance found in the plant) decarboxylates (unpublished) into the active THC, BHO is not orally active and must be vaporized for the users to achieve its effects.(15)
BHO production started out as a dangerous “backyard-chemist” style operation that is famous for causing numerous explosions and house fires. Through the course of legalization, the production has steadily gained sophistication. The most modern, legal extraction laboratories live up to the OSHA standards with full ventilation and butane recovery. Modern techniques also include steps to “de-wax” the product by dissolving the crude BHO in isopropyl alcohol and chilling in a freezer, and, finally, filtering off the precipitated waxes in a process known as winterization. Many subtleties in its production exist, but many remain secretive due to the highly competitive nature of the cannabis marketplace and the general inability of extract producers to file patents due to the drug’s legal status at the federal level.
In addition to butane extraction, supercritical CO2 extraction has gained traction due to the fact that is does not leave any trace of hydrocarbon solvents in the end product.(16) The cannabis extract made by this method, colloquially known as CO2 oil, has a lesser viscosity than BHO, a property that allows it to be used in vaporizer pens on its own with no cutting agents. The lesser viscosity is due to the fact that the supercritical extraction process requires the product to be first decarboxylated (heating in an oven at 100+ °C),(17) leaving an extract consisting of all THC (an oil at room temperature) and no THCA (a solid at room temperature). CO2 oil is generally more expensive than BHO and mostly present on the market in prefilled vaporizer cartridges and not commonly as a standalone extract for dabbing. Because this extraction method does not leave residual hydrocarbons, it has been named, along with alcohol extracts, as the only allowable medical extracts to be sold under the medical cannabis regulations in New York,(18) Minnesota, Ohio, and Pennsylvania.
According to a recent survey,(11) the main reasons for using dabs are that less material is needed to get the desired effect and a “cleaner high.” Consumers consider dabbing to be a form of vaporization, and, therefore, view it as easier on the lungs than smoking.(19) However, little information exists on the prevalence of dabbing. From 213 BHO extraction laboratories in the 17 states raided in 2014, 2015 saw a steep increase in the number of laboratories raided to 337 in 26 states.(20) An analysis of the Twitter content related to dabs found a greater popularity in the states that have legalized recreational and/or medical cannabis.(21)
Different types of nails, the surface on which vaporization occurs, exist on the market. Use of an electrically controlled nail (“e-nail”) allows temperature control; but, more commonly, users heat the nail (made of titanium, ceramic, or quartz) with a crème brulee torch(22) and have no temperature control. A minority of dabbers use lower temperatures to preserve flavor, whereas a majority use higher temperatures to assure complete vaporization with no wasted material. E-nail users posting online cite a preferred temperature around 710 °F (378 °C), but cite a range from 340–482 °C.(23-25) Raber et al. reported a dabbing temperature of 300 °C, but this was only an (low) estimate. The boiling point of THC has recently been predicted to be ca. 417 °C,(26) but vaporization can occur at temperatures lower than this by the use of a “carb cap” that reduces pressure on its surface during inhalation.(27)
This study is an initial effort toward assessing the safety of dabbing cannabis extracts. Due to the fact that these consist of a complex mixture, we have begun our focus on terpenoids, the component we predict to be the most thermally labile. To study dabbing, we carefully recreated the inhalation topography and temperatures employed by users. The study described herein is the first to investigate the degradation products from dabbing and is focused on the terpene fraction of the extracts used by consumers.
Abstract
Inhalable, noncombustible cannabis products are playing a central role in the expansion of the medical and recreational use of cannabis. In particular, the practice of “dabbing” with butane hash oil has emerged with great popularity in states that have legalized cannabis. Despite their growing popularity, the degradation product profiles of these new products have not been extensively investigated. The study herein focuses on the chemistry of myrcene and other common terpenes found in cannabis extracts. Methacrolein, benzene, and several other products of concern to human health were formed under the conditions that simulated real-world dabbing. The terpene degradation products observed are consistent with those reported in the atmospheric chemistry literature.
Topics:
Extraction; Organic compounds and Functional groups; Solvation; Toxicology
Introduction
Terpenes and terpenoids are present in such a wide diversity of environments (nature, food, cosmetics, pharmaceuticals, and drugs) that their consequences for inhalation toxicology cannot be ignored. Additionally, their inclusion in flavored electronic cigarettes(1) and ubiquitous presence in inhalable cannabis products are of particular concern. The medicinal and psychoactive effects of cannabis have been proposed to be enhanced by terpenes, a phenomenon known as the “entourage effect”,(2) and these relatively unsubstantiated assertions of benefits have led the cannabis industry to place a heavy emphasis on these aroma compounds.
Terpenoid degradation in the context of cannabis has not been extensively studied;(3, 4) however, it has attracted attention in the context of atmospheric chemistry.(5, 6) For instance, the reactions of terpenoids with O3 and NOx are well-known, but they are not directly applicable to e-cigarettes or inhalable cannabis products. However, these and other studies of pyrolysis and combustion of terpenoids should serve as a starting point toward understanding the reaction pathways in consumer vaporization devices. Despite the growing popularity of flavored e-cigarettes and terpene-enriched cannabis extracts, the chemical profiles of their terpene degradation products have not been evaluated in detail.
Of very recent concern is the practice of dabbing, which has emerged as a dangerous and rapidly growing trend in cannabis consumption. It consists of inhaling the vapors produced by placing a small amount of cannabis extract (a “dab”) on a small heated surface (the “nail”), which is connected to a water pipe.(7) Its delivery of harmfully large amounts cannabinoids(8, 9) represents a potential danger to consumers, but little is known about the toxicants the process may produce.
The principal extract used in dabbing is butane hash oil (BHO). BHO is a resinous, nonpolar extract of the cannabis made using butane as a solvent.(10) BHO has active ingredient (tetrahydrocannabinol (THC) or cannabidiol) contents ranging between 50 and 90%,(8, 11) with terpene content ranging from 0.1 to 34% (unpublished). Myrcene is unequivocally the most abundant terpene in cannabis, followed by limonene, linalool, pinene, caryophyllene, and humulene; however, the plant can contain up to 68 additional terpenic compounds in trace amounts.(12) Additionally, some consumers increase the terpenoid content by dipping BHO in a vial of terpenes prior to use (“terp dipping”).(13)
BHO is made by passing butane over cannabis buds and leaves, and subsequently “purging” the butane from the product under vacuum at room temperature or in an oven. Different nuances in its processing can lead to slightly different consistencies, which take on terms such as shatter, budder, crumble, pull-and-snap, wax, and so on. In all of its forms, the extract is a sticky, resinous substance similar to the oleo-resins of other plants.(14) Because the process does not involve heating the extract to the point that delta-9-tetrahydrocannabinolic acid (THCA, the native form of this substance found in the plant) decarboxylates (unpublished) into the active THC, BHO is not orally active and must be vaporized for the users to achieve its effects.(15)
BHO production started out as a dangerous “backyard-chemist” style operation that is famous for causing numerous explosions and house fires. Through the course of legalization, the production has steadily gained sophistication. The most modern, legal extraction laboratories live up to the OSHA standards with full ventilation and butane recovery. Modern techniques also include steps to “de-wax” the product by dissolving the crude BHO in isopropyl alcohol and chilling in a freezer, and, finally, filtering off the precipitated waxes in a process known as winterization. Many subtleties in its production exist, but many remain secretive due to the highly competitive nature of the cannabis marketplace and the general inability of extract producers to file patents due to the drug’s legal status at the federal level.
In addition to butane extraction, supercritical CO2 extraction has gained traction due to the fact that is does not leave any trace of hydrocarbon solvents in the end product.(16) The cannabis extract made by this method, colloquially known as CO2 oil, has a lesser viscosity than BHO, a property that allows it to be used in vaporizer pens on its own with no cutting agents. The lesser viscosity is due to the fact that the supercritical extraction process requires the product to be first decarboxylated (heating in an oven at 100+ °C),(17) leaving an extract consisting of all THC (an oil at room temperature) and no THCA (a solid at room temperature). CO2 oil is generally more expensive than BHO and mostly present on the market in prefilled vaporizer cartridges and not commonly as a standalone extract for dabbing. Because this extraction method does not leave residual hydrocarbons, it has been named, along with alcohol extracts, as the only allowable medical extracts to be sold under the medical cannabis regulations in New York,(18) Minnesota, Ohio, and Pennsylvania.
According to a recent survey,(11) the main reasons for using dabs are that less material is needed to get the desired effect and a “cleaner high.” Consumers consider dabbing to be a form of vaporization, and, therefore, view it as easier on the lungs than smoking.(19) However, little information exists on the prevalence of dabbing. From 213 BHO extraction laboratories in the 17 states raided in 2014, 2015 saw a steep increase in the number of laboratories raided to 337 in 26 states.(20) An analysis of the Twitter content related to dabs found a greater popularity in the states that have legalized recreational and/or medical cannabis.(21)
Different types of nails, the surface on which vaporization occurs, exist on the market. Use of an electrically controlled nail (“e-nail”) allows temperature control; but, more commonly, users heat the nail (made of titanium, ceramic, or quartz) with a crème brulee torch(22) and have no temperature control. A minority of dabbers use lower temperatures to preserve flavor, whereas a majority use higher temperatures to assure complete vaporization with no wasted material. E-nail users posting online cite a preferred temperature around 710 °F (378 °C), but cite a range from 340–482 °C.(23-25) Raber et al. reported a dabbing temperature of 300 °C, but this was only an (low) estimate. The boiling point of THC has recently been predicted to be ca. 417 °C,(26) but vaporization can occur at temperatures lower than this by the use of a “carb cap” that reduces pressure on its surface during inhalation.(27)
This study is an initial effort toward assessing the safety of dabbing cannabis extracts. Due to the fact that these consist of a complex mixture, we have begun our focus on terpenoids, the component we predict to be the most thermally labile. To study dabbing, we carefully recreated the inhalation topography and temperatures employed by users. The study described herein is the first to investigate the degradation products from dabbing and is focused on the terpene fraction of the extracts used by consumers.
