Extracts and tinctures of cannabis

Substance identification
Extracts and tinctures of cannabis are preparations that have been extracted from the leaves and flowers of Cannabis sativa. They include cannabis oils, teas and Sativex® (an extract with approximately equal quantities of Δ9-THC and cannabidiol). Cannabis undergoes an extraction process in order to separate the desired compounds such as cannabinoids from the undesired products. Extracts can exhibit variations of shade of colour, taste, smell and consistency, ranging from a runny oil to a solid depending on the manufacturing process. They can also take the form of alcohol or aqueous preparations.

Cannabis extracts may be delivered through various routes of administration, including sublingual, oral, inhalation (smoking or vaping), rectal and transdermal. "Dosage" of cannabis extracts most often refers to the amount of Δ9-THC contained in the preparation. Tinctures are usually administered sublingually or added to edibles or beverages for oral consumption. Oils may be incorporated into food or beverages for oral administration or may be vaped or "dabbed" (inhalation of vapour from a heated preparation). Sativex® is formulated into an oromucosal spray.

Oils
Oils can be produced with a range of Δ9-THC concentrations. Those with the highest concentration are butane hash oil and propane hash oil, which may contain from 50 to 90% of the active ingredient, Δ9-THC. Oils with high concentrations of cannabidiol can also be produced by extraction using a variety of methods. Some oils, such as essential oil and hemp seed oil, do not contain significant concentrations of Δ9-THC or cannabidiol.

Cannabis oil extracts can also be incorporated into a wide range of food products.

Aqueous extracts
An aqueous extract of C. sativa is often referred to as a tea. The addition of boiling water is a simple and probably one of the oldest methods for preparing a cannabis extract for oral administration. The amount of Δ9-THC extracted using this method is significantly lower than what would be obtainable using other methods.

Sativex®
Sativex® is a unique cannabis extract with an approximate 1:1 ratio of Δ9- THC to cannabidiol, as the principal cannabinoids, together with other minor cannabinoids delivered as an oromucosal spray approved for medical purposes.

WHO review history
Cannabis extracts and tinctures of cannabis are listed in Schedule I of the Single Convention on Narcotic Drugs, 1961.

Cannabis extracts and tinctures were pre-reviewed at the fortieth meeting of the ECDD and were recommended for critical review.

Similarity to known substances and effects on the central nervous system
Effects produced by Δ9-THC-rich cannabis extracts, tinctures, oils and tea are similar to those observed with Δ9-THC, but, as noted above, the effects may be more pronounced and associated with a greater risk of adverse effects, such as cardiovascular effects, when extracts with high Δ9-THC concentrations are inhaled.

The most common adverse effects of Sativex® are mild to moderate dizziness and fatigue. Transient adverse effects such as increased heart rate and blood pressure, disorientation, depression, euphoria, transient psychotic reactions and dissociation have also been reported.

Dependence potential
The psychoactive constituent, Δ9-THC, present in most of the extracts, has been shown to have dependence potential, as supported by numerous animal and human studies. There is evidence that regular use of certain cannabis extracts with high concentrations of Δ9-THC, such as butane hash oil, increases the probability and severity of dependence.

Actual abuse and/or extent of abuse
There is little epidemiological information on the extent of use of cannabis extracts. The information that is available suggests that extracts in the form of oil or wax containing high levels of Δ9-THC are used by a minority of cannabis users. However, this rate may be increasing and the use of such extracts appears to be associated with higher levels of physical dependence on cannabis.

Information on the toxicology of cannabis extracts, tinctures, oils and tea is also very limited. The toxicity produced by Δ9-THC-rich cannabis extracts, tinctures, oils and tea is similar to the toxicity of Δ9-THC. However, as noted above, the effects may be more pronounced, with a greater risk of adverse effects, when extracts with high Δ9-THC concentrations are inhaled.

Depending on the method used to produce it, cannabis extract may contain residual solvents (naphtha, isopropanol, acetone, hexane, ethyl alcohol or butane), which are harmful if ingested by the user and may cause serious burns when ignited. Some extracts contain contaminants such as pesticides. Thinning agents such as propylene glycol and polyethylene glycol 400 (used to smooth the flow of viscous cannabis oils from vaping cartridges) can produce high concentrations of toxic acetaldehyde and formaldehyde when heated in certain devices. In addition, terpenes can be converted to the toxic degradants methacrolein (an irritant) and benzene (a carcinogen).

Vaping and smoking are known to produce rapid psychoactive effects. However, the abuse potential of high-potency cannabis extracts administered via vaporizing has not been studied in humans.

A clinical trial to evaluate the abuse potential of Sativex® in recreational cannabis users showed that high doses of Δ9-THC induced cannabis-like effects, but this did not occur at a lower dose. Abuse has not been reported in post-market surveillance of Sativex®. However, euphoria has been reported as an adverse effect of Sativex®.

Therapeutic usefulness
Sativex® has been granted marketing authorizations for treatment of spasticity due to multiple sclerosis in several countries, and for treatment of neuropathic pain in multiple sclerosis and chronic cancer pain. Sativex® is being investigated for a variety of other indications including, but not limited to, anxiety disorder, cannabis use disorder, attention-deficit/hyperactivity disorder, and depression and sleep disorders.

Cannabis extracts and tinctures are not listed on the WHO EML (twentieth list) or the WHO Model List of Essential Medicines for Children (sixth list).

Recommendations
Extracts and tinctures of cannabis include preparations that are produced by application of solvents to cannabis, and they are currently in Schedule I of the 1961 Single Convention on Narcotic Drugs. Extracts and tinctures include both medical preparations, such as that containing an approximately equal mixture of Δ9-tetrahydrocannabinol (dronabinol; Δ9-THC) and cannabidiol and nonmedical preparations with high concentrations of Δ9-THC such as butane hash oil. While the medical extracts and tinctures are administered orally, nonmedical preparations such as butane hash oil are normally inhaled through vaporization. There are also extracts with no psychoactive effects that contain cannabidiol.

The Committee recognized that the term "extracts and tinctures of cannabis" as cited in the 1961 Single Convention on Narcotic Drugs encompasses these diverse preparations some of which have psychoactive properties and some which do not. The Committee also recognized that the variability in psychoactive properties of these preparations is due principally to varying concentrations of Δ9-THC, which is currently scheduled in the 1971 Convention on Psychotropic Substances, and that some extracts and tinctures of cannabis without psychoactive properties, and including predominantly cannabidiol, have promising therapeutic applications.

As per the 1961 Single Convention on Narcotic Drugs, preparations are defined as mixtures, solid, or liquid containing a substance in Schedule I or II and are generally subject to the same measures of control as that substance. The Committee noted that, by this definition, the 1961 Single Convention on Narcotic Drugs may cover all products that are "extracts and tinctures" of cannabis as "preparations" of cannabis and also, if the Committee`s recommendation to move dronabinol to Schedule I of the 1961 Single Convention on Narcotic Drugs was adopted, as "preparations" of dronabinol and its stereoisomers.

Recommendation: The Committee recommended deleting "extracts and tinctures of cannabis" from Schedule I of the 1961 Single Convention on Narcotic Drugs.

The Committee acknowledged that the fact that diverse preparations with a variable concentration of Δ9-THC are controlled within the same entry "extract and tinctures" under the same Schedule, is a challenge for the authorities responsible for implementing control measures in their respective countries.