Cannabis is the most used illicit drug worldwide, with an estimated 200 million users (approximately 4% of the world's population) between the ages of 15 and 64 in 2019 (1). In Europe, it is also the most widely used drug, with a prevalence of daily use of 1.8% in the general population and 10.3% in individuals between 15 and 24 years of age, respectively (2).

In recent years, synthetic cannabinoids (SCs) have emerged as substitutes for natural cannabis as they are cannabinoid types 1 and 2 receptor agonists similar to tetrahydrocannabinol (THC), the main psychoactive component of cannabis, which is a partial agonist (3). The most common products containing SCs are smoking mixtures, e-liquids, and infused paper (4). Some effects of SCs intoxication are loss of consciousness, respiratory depression, and behavioral alterations such as aggression or self-injury (5). Over the years, different generations of SCs have appeared, each time showing a higher potency than THC, making them attractive to some consumers (3, 6). Recently, a fourth generation of SCs has been described, which could cause serious damage to health based on its pharmacological and toxicological activity (7). The effects experienced may differ between SC users, as in the case of cannabis use, including feelings of euphoria, relaxation, or even paranoia (5); however, they are usually more intense than those experienced with natural cannabis (8).

SCs were first synthesized in 1970 in an attempt to find new analgesics for pain treatment, but it was not until the 2000s that they appeared in the market (9). The popularity of these compounds was boosted in 2004 by the emergence of a new product called “Spice” (4). A few years later, in 2008, the first cases of poisoning related to SCs use were reported (4), some of which resulted in fatal overdoses (10). Since 2008 to date, the European Union Early Warning System controls 209 different SCs; thus, SCs are the largest group of new psychoactive substances (NPS) monitored (2, 4).

Cannabis is commonly used by patients with opioid use disorder (OUD) (11), which points to this population as a potential consumer of SCs. Other SC users include regular cannabis users, people who experiment with new drugs (e-psychonauts), increasingly vulnerable groups, such as high-risk users (4, 12), and men aged between 13 and 59 with a history of polydrug use who consider SCs a good alternative to cannabis (13). Since SCs are not detected in the standard toxicological urine tests used in clinical practice, they can be easily used by individuals for pleasure and enjoyment (13).

Notably, the prevalence of SC use is <1% in the European general population, but this is higher if we focus on subpopulations such as young adults or psychiatric patients, especially those with psychosis (4). The national survey among the Spanish general population shows a prevalence of SC use of the 0.6% and increases to 1.2% in the group aged between 25 and 34 years (14).

OUD individuals have not been the focus population for studying these substances, which are more likely to be present in recreational settings, such as music festivals or raves, or among e-psychonauts. In the present study, we investigated the use of natural and synthetic cannabis in an OUD population from Barcelona through urinalysis.