Marijuana specifically refers to the plant. You’re asking about synthetic cannabinoids.
A cannabinoid is simply any substance that binds to the cannabinoid receptors. Cannabinoids can be classified into 3 groups:
- Endocannabinoids aka the endogenous ligands our body naturally produces to bind to our cannabinoid receptors. Termed EC
- Phytocannabinoids aka marijuana derived cannabinoids from plant sources. Termed PC. Cannabis contains about 120 different phytocannabinoids but the two most prominent are THC and CBD.
- And synthetic cannabinoids. Termed SC
Where did SC’s come from?
The major subclass of SC’s (cyclohexylphenols) where first synthesized in the late 70s and early 80s by Pfizer as they were trying to create more powerful analgesic analogues to THC. They started with CP 47,497 which they then extended the dimethylheptyl side chain to a dimethyloctyl side chain.
While the idea of using it clinically was dropped it was marketed as a research molecule because it had high binding to the cannabinoid receptor.
The homologue known as JWH-018 was first detected in 2008 by forensic chemists.
Why are SC’s so dangerous?
The biggest difference between PC’s and SC’s is that PC’s are not full agonists to the cannabinoid receptors. THC Is a partial agonist and CBD Is a antagonist. SC’s however are FULL cannabinoid receptor agonist. Full agonist activity.
For example:
JWH-018 is a synthetic CB, which is a full agonist to CB1 and CB2 receptors and can cause hallucinations, vertigo, paresthesias, shaking, shivering, hypertension, dry mouth, vomiting, mydriasis, hypokalemia, extrasystoles, tachycardia and conjunctival hyperemia
Renal injury
Full agonist binding to cannabinoid receptors in the nephron has been shown to activate pathways like MAPK, P38, c-Jun N-terminal kinase pathways thus inducing cellular apoptosis or necrosis.
Cardiac injury
SC induce instantaneous release of norepinephrine. SC also induce reflexive cardiac weakness.
Neurological injury
Contrary to THC and CBD which are anticonvulsants SC’s are the opposite; in a study of 44 individuals who presented at the ER for SC toxidrome 12.5% experienced generalized seizure. It’s likely that full agonism of the CB1 receptor possibly induces a post activation lull or that full agonist activity at the CB1 receptor is intrinsically pro convulsant. Or the long lived metabolites of some Sc’s are classic proconvulsants.
Psychiatric disturbances
While there is a very weak link between thc use and the emergence of psychosis in predisposed or individuals who have had psychosis in the past SC’s are associated with inducing psychosis in otherwise non predisposed individuals. SC’s result in much more paranoia and anxiety. They are linked to suicidal ideation and suicide. Likely this is because of the indirect modulation the endocannabinoid system has on dopamine pathways.
Possible solutions?
Honestly I think legalize marijuana plant as well as decriminalize possession of phytocannabinoids including THC and CBD. Keep synthetic cannabinoids Schedule II but remove their status as legal analogues and center them as the prototypical class instead of the current situation of placing phytocannabinoids as the prototypical substance for legislation.
Produce easy to access and affordable synthetic cannabinoid testing kits for mass use at the law enforcement level. Even one kit with 5 slots corresponding to the 5 classes of SC’s. Start a program teaching a test for 1 test for all as often more than 1 SC often is mixed in a “spice” packet.
Further details on the Subject:
Marijuana and its active ingredients possess anticonvulsant effects in animal models and humans. For centuries, prior to the development of AEDs, marijuana and hashish were used to treat epilepsy and are still utilized in countries with limited access to AEDs. Through mechanisms that have not been fully elucidated cannabinoids decrease both glutamate and γ-aminobutyric acid (GABA) synaptic transmission in the brain. Decreasing the excitatory neurotransmitter glutamate decreases seizure susceptibility, while decreasing the inhibitory neurotransmitter GABA increases seizure susceptibility.
Like THC and CBD, synthetic cannabinoids have nonpolar, lipid-soluble structures that are relatively volatile. Several categories exist, including THC analogues (eg, HU-210), cyclohexylphenol compounds (eg, CP-47,497), and aminoalkylindole compounds developed by J. W. Huffman (eg, JWH-018). Despite the basic structural similarities with THC, the heterogeneous synthetic cannabinoids will not cross-react with traditional THC detection methods.
Chemical analysis of Spice products continues to yield synthetic cannabinoids that are distinct from the 5 compounds recently banned. In 2009, 1 month after Germany passed legislation banning JWH-018 and several other compounds, Spice products emerged that contained JWH-073, a synthetic cannabinoid that was not included in the legislation. A large inventory of previously synthesized cannabinoids are candidates for future Spice production. The toxicity of the synthetic cannabinoids, plant matter, and unknown adulterants used in the production of Spice causes side effects which are not typically encountered following marijuana use, such as psychosis, elevated blood pressure, tachyarrhythmia, hyperactive agitation, and seizure. As a result, Spice products are receiving an increasing amount of attention in EDs and poison control centers, but numerous cases are missed because commercially available drug tests do not detect synthetic cannabinoids, which may be a large part of the products' appeal.
Side Effect of Synthetic Marijuana
Mild impairment of memory
Changes in perception
Tingling
Tremors
Rapid heartbeat
Suicidal thoughts
Calmness
Relaxation
Euphoria
Slurred speech
Poor coordination (ataxia)
Greater creativity
A feeling of wellbeing
Psychological side effects are:
Psychosis
Hallucinations
Anxiety
Severe psychomotor agitation
Delirium
Paranoia
Withdrawal symptoms of Synthetic Marijuana (Spice)
Tremors
Nightmares
Heavy sweating
Diarrhea
Vomiting
Insomnia
Headaches
Extreme fatigue
Problems thinking clearly
Neglecting responsibilities
Loss of interest in activities
This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.
© 2022 Adetoro Abdulhakeem
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