Hexahydrocannabinol

Substance identification 

Hexahydrocannabinol (IUPAC name: 6,6,9-Trimethyl-3-pentyl-6a,7,8,9,10,10a- hexahydrobenzo[c]chromen-1-ol), also known as HHC, has three stereogenic centres, indicating that eight stereoisomers are possible. As a semi-synthetic cannabinoid, however, it is usually found as a mixture of (6aR,9S,10aR)-6,6,9- trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol (9S epimer) and (6aR,9R,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydrobenzo[c] chromen-1-ol (9R epimer). 

Hexahydrocannabinol has been described as a colourless viscous oil or resin that changes to dark orange after exposure to oxygen. Hexahydrocannabinol- containing products include low- tetrahydrocannabinol (THC) cannabis flowers and resins infused or sprayed with the substance, e-liquids and cartridges for electronic cigarettes, edible products such as gummies and marshmallows, tinctures resembling dietary supplements and distillate oils. The routes of administration include inhalation, oral and sublingual. 

WHO review history 

Hexahydrocannabinol has not previously been reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention that this substance is manufactured clandestinely, poses a risk to public health and has no recognized therapeutic use. 

Similarity to known substances and effects on central nervous system 

The (9R)-hexahydrocannabinol epimer has CB1 and CB2 receptor binding affinity similar to that of delta-9-THC. Hexahydrocannabinol acts as a partial agonist at the CB1 receptor, as does delta-9-THC, and produces psychoactive effects, including adverse effects, similar to those produced by delta-9-THC. In animals, it has been shown to produce behavioural effects consistent with delta-9-THC. In humans, sleepiness, euphoria, anxiety, agitation, psychosis, tremors and disorientation were reported, in addition to respiratory, cardiovascular and gastrointestinal effects. Hexahydrocannabinol is found in trace amounts as a phytocannabinoid in cannabis plants but is usually synthesized from cannabidiol. 

Dependence potential 

No studies of the dependence potential of hexahydrocannabinol in animals or humans have been reported. Its effects at CB1 receptors suggest that it would produce dependence similar to that produced by other cannabinoid partial agonists such as delta-9-THC. Withdrawal effects have been reported in humans, and multiple countries have reported that people who use hexahydrocannabinol have presented for treatment of drug dependence. 

Actual abuse and/or evidence of likelihood of abuse 

No studies have been reported in animals or humans on the likelihood of abuse of hexahydrocannabinol; however, CB1 receptor agonists have known abuse potential. 

Adverse effects including emergency departments presentations for non-fatal intoxications, with symptoms such as dizziness, confusion, unconsciousness, psychosis (hallucinations, delusions and paranoia), anxiety, panic attack, depression, hypertension, nausea and vomiting, similar to those seen with delta- 9-THC. 

Hexahydrocannabinol has been analytically confirmed in people driving under the influence of drugs and in clinical admissions for drug intoxication in adults and children in multiple countries, including cases in which hexahydrocannabinol was confirmed to be the only substance involved. Seizures of hexahydrocannabinol have been reported in many countries in a number of regions. 

Therapeutic usefulness 

Hexahydrocannabinol is not known to have any therapeutic use. 

Rationale and recommendation 

Hexahydrocannabinol [IUPAC name: 6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a- hexahydrobenzo[c]chromen-1-ol], also known as HHC, is a semi-synthetic cannabinoid receptor agonist with a mechanism of action and effects similar to those of delta-9-tetrahydrocannabinol, which is controlled under Schedule II of the Convention on Psychotropic Substances of 1971. There is sufficient evidence that hexahydrocannabinol is used in such a way as to constitute a public health and social problem, warranting placement under international control. 

The Committee recommended that hexahydrocannabinol [IUPAC name: 6,6,9-Trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol], be added to Schedule II of the Convention on Psychotropic Substances of 1971.