Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with D9-Tetrahydrocannabinol
Synthetic cannabinoids are commonly used as recreational drugs. However, an increasing number of clinical reports have documented seizures and even death following synthetic cannabinoids use. Therefore, the need to examine the effects of these compounds on various biological systems is urgent.
In a recent study, scientists employed mice to compare the toxicity of several synthetic cannabinoids, AM-2201, CP55940, JWH-073, HU-210 with THC and cannabidiol – a psychoactive and a non-psychoactive constituent of the plant cannabis, respectively. Mice were given daily injections of each of these compounds and assessed for convulsion and hypothermia, or decrease in body temperature – symptoms corresponding to seizures in humans. The study results indicated that AM-2201 and JWH-073 produced significantly more convulsions and all synthetic cannabinoids produced significantly more hypothermia than THC and CBD.
To follow-up, the researchers pre-treated mice with either a blocker of the cannabinoid receptor type 1 (CB1) or a blocker of the cannabinoid receptor type 2 (CB2), and then administered similar doses of the above compounds. While both are bound and activated by cannabinoids, CB1 is widely expressed in the brain and CB2 in cells of the immune system. The researchers found that when CB1 was blocked, the convulsions and hypothermia induced by most compounds were prevented but this was not the case for CB2. Such data suggested that the synthetic cannabinoids exert their adverse effects through activation of receptors in the brain, although the exact mechanisms remain a topic of further study.