Synthetic and Non-synthetic Cannabinoid Drugs and Their Adverse Effects-A Review From Public Health Prospective

Abstract

There is a growing use of novel psychoactive substances containing synthetic cannabinoids. Synthetic cannabinoid products have effects similar to those of natural cannabis, yet, these drugs are more potent and dangerous, and have been associated with dangerous adverse effects. Here, we review current literature on the epidemiology, acute, and chronic effects of synthetic and natural cannabinoid-based drugs. Synthetic drugs contain a mixture of psychoactive compounds that mostly bind cannabinoid receptors with high potency. These synthetic drugs replicate the effects of natural cannabis and Δ9-tetrahydrocannabinol but they induce more severe adverse effects including respiratory difficulties, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Chronic use of synthetic cannabinoids has been associated with serious psychiatric and medical conditions and even death. Given the growing popularity in the use of cannabinoid-based drugs and their harmful potential, there is a need for further research in this field.

Adding more “spice” to the pot: A review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists

“…From an epidemiological perspective, Cohen and Weinstein have recently highlighted that the lifetime prevalence of SCRA use in the general global population is between 0.2% and 4% . When compared with the lifetime use of cannabis (ranging between one quarter and one third of the global population), SCRA use currently appears to be lower .…”

“…Although the latter herbal blends were labelled as being "not for human consumption", it soon became apparent that these products were being misleadingly marketed as cheap, safe, and legal alternatives to illicit cannabis. 8 While such herbal blends listed only plantbased ingredients, including damiana (Turnera diffusa) and Lamiaceous herbs, it is now understood that the psychoactive effects associated with the recreational use of these herbal mixtures are due to the presence of SCRAs. In a manner similar to the consumption of illicit cannabis, SCRA-containing herbal blends are typically rolled in a cigarette or "joint" and smoked.…”

“…8,14 When compared with the lifetime use of cannabis (ranging between one quarter and one third of the global population 14 ), SCRA use currently appears to be lower. 8 More recent evidence from a study investigating SCRA use among college students (n = 1140) in the United States indicates that the availability, legislative control status, and poor detectability in drug screening tests are common incentives for SCRA use in this population. 15 Importantly, the growing use of SCRAs among vulnerable and marginalized population groups, including homeless and incarcerated individuals, is a growing cause for concern and has been highlighted in recent literature.…”

“…[32][33][34][35] At present, it remains unclear if this presence of 9 in certain batches of SCRA-F I G U R E 1 JWH-018 (1) and the C-8 homolog of CP-47,497, cannabicyclohexanol (2), were first detected in herbal blends in 2008 1 and were later followed by other indole-(3) and indazole-3carboxamide (4) cannabinoid ligands. However, SCRAs have now evolved to incorporate azaindole (5), γ-carbolinone (6), and carbazole (7) heterocyclic core structures F I G U R E 2 The indazole SCRA, AMB-FUBINACA (8), was found to be responsible for a mass intoxication in New York in 2016. 4 Recent evidence suggests that some SCRA-containing products are now contaminated with the potent vitamin K antagonist brodifacoum (9).…”

Modulatory effects of cannabinoids on brain neurotransmission

“…In contrast to Δ9‐Tetrahydrocannabinol (Δ9‐THC) which is the main psychoactive constituent of cannabis, SCs are more potent and efficacious at cannabinoid CB 1 and CB 2 receptors (Pertwee, ; Bhattacharyya et al ., ; Castaneto et al ., ). Therefore, although SC drugs are designed to mimic the effects of cannabis, they induce more severe and persistent adverse effects since they include more potent and toxic psychoactive compounds than traditional cannabis (Fattore, ; Cohen et al ., ; Cohen & Weinstein, ,b; Langer et al ., ; Shalit et al ., ; van Amsterdam et al ., ; Weinstein et al ., ).…”