Delta-9-tetrahydrocannabinol (D9-THC) is the driving cannabinoid which gives users its psychoactive effects. However, the cannabis plant contains over 400 individual chemicals, many with unique pharmacological properties.
Cannabis has been cultivated for millennia for materials and oils but has been restricted over the past century due to its psychoactive effects.
The collection of synthetic cannabinoids, manmade chemicals designed to act at cannabinoid receptors, continues to grow.
In recent years there has been a rise in popularity of these alternative cannabinoids and this trend is likely to continue with the continuing legalisation of recreational cannabis throughout the US.
Due to cannabinoids increasing popularity, it is vital for physicians and healthcare providers to be aware of the different products available.
Throughout this article, common cannabinoids will be identified, their legality and the overall clinical response to their use will be discussed.
DELTA-9 (∆9-THC):
- Most abundant psychoactive cannabinoid.
- Directly extracted from the cannabis plant, contrasting to other alternative cannabinoids which are chemically modified.
- The effects are dose dependent
- The concentrations of cannabis products are typically described by the amount of ∆9-THC per dry weight.
- Average cannabis potency today is estimated to be 20%, a gram of cannabis is 200mg of ∆9-THC.
- Psychoactive effects are driven through the forementioned CB1 receptor, leading to adenylyl cyclase inhibition.
CANNABIDIOL (CBD):
- Huge increase in CBD-labelled health products in recent years due to its proposed benefits.
- Global market of CBD is estimated to reach US $47 billion by 2028
- Commonly taken orally or as a topical cream, CBD has been shown to have analgesic and anti-inflammatory effects by acting as a cyclooxygenase and lipoxygenase inhibitor.
- Low affinity for the forementioned CB1 and CB2 receptors.
- Highly hepatically metabolised.
- Recommended that patients receiving CBD have their bilirubin and transaminase levels monitored before and during treatment to assess for hepatotoxicity.
DELTA-8 (∆8-THC):
- Nearly identical to ∆9-THC, difference is the location of a single carbon double bond. This factor is enough to drive its divergent psychoactive properties.
- Stronger affinity for CB1 receptor than ∆9-THC.
- ∆8-THC is roughly half as potent as ∆9-THC.
- Taken orally but typically smoked.
- Can naturally be extracted from cannabis plant, it is found in such small quantities that the process isn’t economical, so the most available product is formed through a conversion process from CBD with the use of acids.
- Important for clinicians to recognise that available products are often not pure ∆8-THC.
- Common immunoassays cannot note the difference between ∆8-THC and ∆9-THC so patients will test positive for THC after using either isomer.
- Little research to investigate the pharmacokinetic profile. However based on limited data, its distribution around the body unsurprisingly appears to be like that of ∆9-THC.
DELTA-10 (∆10-THC):
- Also an isomer solely differing in the location of its double carbon bond.
- Isn’t typically found as a natural component of cannabis but has been known since the 1980s when it was first synthesised.
- It can be synthesised directly from ∆9-THC.
- Formed as an impurity when ∆8-THC is synthesised from CBD.
- Shown to bind and utilise the same CB1 and CB2 cannabinoid receptors throughout the body.
- Little data regarding this alternative cannabinoid, most data deem it to be less potent than ∆9-THC.
- ∆10-THC will lead to a positive THC immunoassay drug test in patients.
THC-P (Tetrahydrocannabiphorol):
- Highest potency cannabinoid naturally found in both hemp and cannabis is THC-P.
- THC-P has potencies up to 33 times that of ∆9-THC.
- Differences are hypothesised to be secondary to additional carbon atoms within its alkyl side chain.
- Most cannabinoids have a pentyl side chain, THC-P has two additional carbon chains.
- Highest binding affinity to CB1 receptors.
- Research into mice has indicated similar cannabimimetic activity to ∆9-THC – analgesia, hypomobility and decreased temperature.
- THCP breakdown within the body leads to THC-COOH (same metabolite formed by ∆9-THC)
- Users of THC-P would have a positive immunoassay standard THC drug screen.
THC-O (O-Acetyl-∆9-THC):
- An alternative cannabinoid not naturally found within the cannabis plant.
- Available in vape cartridges, edibles and tinctures.
- Potency is up to 3 times that of ∆9-THC.
- The only cannabinoid to have reported pseudo-dissociative effects and in high doses patients may present like they have consumed hallucinogenic drugs.
- Further research needs to be performed to fully elucidate its effects and pharmacokinetics.
CANNABINOL(CBN):
- First compound to be isolated from cannabis extract.
- Naturally found as a degradation product from ∆9-THC as it oxidises.
- Average cannabis plant ranges between 0.1-1.6%
- CBN has higher affinity to CB2 receptors than CB1
- CBN does not have any double bond isomers or stereoisomers.
- Shown initial promise as a sleep aid in patients.
Future alternative cannabinoids:
Additional cannabinoids that may increase in popularity include cannabigerol (CBG) and cannabichormene (CBC). CBG found in small qualities in cannabis is sold as a dietary supplement. CBC has begun to show promising results regarding anti-inflammatory properties.
Alternative cannabinoids are typically used by young adults and have been increasing in frequency over the past years.
It is vital for medical providers to stay up to date regarding different cannabinoid properties in order to best evaluate and treat patients.
Source: http://www.rimed.org/rimedicaljournal/2022/09/2022-09-37-report-volpe.pdf?mc_cid=178794138b&mc_eid=96c196b96d
