Synthetic and Non-synthetic Cannabinoid Drugs and Their Adverse Effects-A Review From Public Health Prospective, Koby Cohen and Aviv M. Weinstein, 2018

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

Koby Cohen and Aviv M. Weinstein

Frontiers in Public Health, 2018, Volume 6 | Article 162

doi : 10.3389/fpubh.2018.00162

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 19-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.

Keywords : cannabis, synthetic cannabinoids, novel psychoactive drugs, drug abuse, addiction



Cannabis is the most widely available and used drug across the world (1, 2). According to the United Nations Office on Drugs and Crime (UNODC) 4% of the global adult population have used cannabis in their life. In the United States of America (USA) alone, 11% (36 million people) of adults used cannabis at least once in their past (3). In addition, the therapeutic use of cannabis and its derivatives is increasing and has been evaluated for a various health conditions including; pain, anorexia, side-effects of chemotherapy, multiple sclerosis, and muscle spasms (4–6). The primary psychoactive constituent within cannabis is1-9 tetra-hydro-cannabinol (THC), which interacts with CB1 and CB2 receptors and it consequently elicits its main effects (7–9). Novel Psychoactive Substances (NPS) which contain Synthetic Cannabinoids (SCs) have recently started to be used recreationally, especially by young adults (10, 11). In contrast to the decline in use of many NPSs such as the cathinones and piperazines, it appears that the number of SC users is increasing (12). Although SC drugs mimic the psychotropic effects of cannabis, their undesired effects are unpredictable and more severe than those associated with cannabis (10, 13–16). Although, there is an increasing interesting on the therapeutic potential of cannabinoid-basedmedications (6, 17) repeated exposure to cannabinoid-agonists in either organic or synthetic forms is associated with both physically and psychological adverse effects (2, 10, 15, 18).

The most notorious psychological side effects are mental disorders including psychotic-states, schizophrenia, and affective disorders (1, 2, 10). The aim of the current review is to describe the available knowledge regarding acute and repeated consumption of both organic and synthetic cannabinoid drugs and their side effects from a public health prospective.


According to national and regional representative surveys, lifetime prevalence of SC use in the general population is between 0.2 and 4% (19). By comparison, lifetime use of cannabis tends to be greater; and to range between one-quarter to one-third of the population (1). However, Winstock and Barratt reported that SC products are widely popular among recreational cannabis users (20). Among high school seniors in USA, the annual prevalence of SC usages was higher than any other drugs, with the exception of cannabis (21). Evidence accumulated from several surveys shows that between 6 and 17% of college students in USA have used SC drugs at least once during their study period (22, 23). Other than that, SC use was relatively frequent among adolescents and young-teenagers. Approximately 1% of
European people between the ages of 14–18 used SC drugs at least once in their lifetime (24). This is especially important since both clinical and preclinical studies indicate that exposure to SC as well as THC during adolescence is associated with an increased risk of developing schizophrenia later in life (25–27) (see Table 1 for comparison of cannabis and SC adverse effects).

Prompted by the alarming growth of the SC drugs phenomenon, legal measures to control the distribution of these drugs have been taken in many countries (57, 58). For example, in the United Kingdom (UK), “first generation” SCs were controlled in 2009 and further legislation to control so-called “second generation” of SCs drugs was enacted in 2013. Yet, subsequent manipulation of the chemical structure of these compounds has resulted in a novel generation of SC’s that are not currently legally controlled in the UK (57). Unfortunately, a similar pattern was observed in other countries as well, manufacturers of SCs are aware of the chemical analog loopholes in the law and continue to manipulate SCs as necessary to keep them legal for distribution (26, 57–59). In line with this, a recent epidemiological study by Waugh et al. (57) reported substantial increase in SC drug use in 2011 despite prior legislation efforts. Suggesting, that legislation efforts alone have an insufficient effect on the distribution and use of SC drugs, and further prevention efforts are required to control this phenomenon

Naive consumers typically report using SCs for various reasons, such as curiosity, high availability, easy access, and lower costs compared with cannabis. Since SCs are mostly undetectable via a simple urine test, a major motivation for consuming SC drugs is the desire to experience “cannabislike” effects without the danger of being detected (11). Other motivations to use SCs are their relatively high availability and low prices (11, 19). In in contrast to cannabis, these synthetic drugs are typically not designed to be mixed with tobacco, probably to achieve the most intense effects (13).