11-nor-9-carboxy-THC

Not to be confused with Tetrahydrocannabinolic acid.

11-nor-9-Carboxy-THC, also known as 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, 11-COOH-THC, THC-COOH, and THC-11-oic acid, is the main secondary metabolite of THC which is formed in the body after Cannabis is consumed.

11-COOH-THC is formed in the body by oxidation of the active metabolite 11-Hydroxy-THC by liver enzymes. It is then metabolized further by conjugation with glucuronide,[1] forming a water-soluble congener which can be more easily excreted by the body.[2]

11-COOH-THC is not psychoactive itself, but has a long half-life in the body of up to several days (or even weeks in very heavy users),[3][4][5] making it the main metabolite tested for when blood or urine testing for cannabis use. More sensitive tests are able to distinguish between 11-OH-THC and 11-COOH-THC, which can help determine how recently cannabis was consumed;[6][7] if only 11-COOH-THC is present then the cannabis was used some time ago and any impairment in cognitive ability or motor function will have dissipated, whereas if both 11-OH-THC and 11-COOH-THC are present then the cannabis was consumed more recently and motor impairment may still be present.

Some jurisdictions where cannabis use is decriminalized or permitted under some circumstances use such tests when determining whether drivers were legally intoxicated and therefore unfit to drive, with the comparative levels of THC, 11-OH-THC and 11-COOH-THC being used to derive a "blood cannabis level" analogous to the blood alcohol level used in prosecuting impaired drivers.[8] On the other hand in jurisdictions where cannabis is completely illegal, any detectable levels of 11-COOH-THC may be deemed to constitute driving while intoxicated, even though this approach has been criticized as tantamount to prohibition of "driving whilst being a regular user of cannabis" regardless of the presence or absence of any actual impairment that might impact on driving performance.

While 11-COOH-THC does not have any psychoactive effects in its own right, it may still have a role in the analgesic and antiinflammatory effects of cannabis,[9][10] and has also been shown to moderate the effects of THC itself which may help explain the difference in subjective effects seen between occasional and regular users of cannabis.[11][12]

Effects

THC has mild to moderate analgesic effects, and cannabis can be used to treat pain by altering transmitter release in the spinal ganglia of the spinal cord and in periaqueductal gray. Other effects include relaxation, impaired senses, visual, auditory, and olfactory fatigue, and appetite stimulation. It has antiemetic properties and also may reduce aggression in certain individuals. Due to its partial agonist activity, THC appears to result in greater downregulation of cannabinoid receptors that endocannabinoids, further limiting its effectiveness over other cannabinoids. While tolerance may limit the maximum effects of certain medications, the evidence suggests that tolerance develops irregularly to different effects with increased resistance to the major side effects, and may actually serve to improve the therapeutic window of the drug. However, this form appears to be irregular tolerance in all areas of the mouse brain and warranted further investigation. THC, and other cannabinoids which contain a phenol group possess a mild antioxidant activity sufficient to protect the neurons against oxidative stress such as is caused by glutamate-induced excitotoxicity.

References