Synthetic cannabinoids (SCs) are psychoactive substances that are gaining popularity for their availability and lack of detection by standardized drug tests. Although some users may perceive SCs as safer alternatives to marijuana, some SCs are more potent and result in more severe toxicities.
Keywords: synthetic marijuana, synthetic cannabis, synthetic cannabinoids, cannabinoids, designer drugs, street drugs, toxicity, hemorrhage, bleeding, K2, spice
Methods
A search of the literature was conducted in the PubMed and SciFinder databases. Results in PubMed were limited to human studies, and only articles in English were included.
Results
Cannabimimetics (synthetic cannabinoids) exhibit agonistic activity on the two cannabinoid re-ceptors, CB1 and CB2 but have no structural similarity with the active compound of marijuana; tetrahydrocannabinol (THC). They are called synthetic cannabinoids due to their mechanism of pharmaceutical actions. Because these compounds have no structural similarity with THC, as expected immunoassays designed to detect marijuana metabolite THC-COOH cannot detect the presence of these drugs or metabolites in urine. These compounds have been classified into several different major classes: carbazoles, classical cannabinoids, cyclohexylphenols, endogenous cannabinoids, indoles, indazoles, pyrroles, the URB-class, and others in a miscellaneous class. Every year, new synthetic cannabinoids arise, differing by the addition or removal of a substituent group. Currently over 130 synthetic cannabinoids have been identified. Although liquid chromatography combined with mass spectrometry or tandem mass spectrometry is commonly applied for analysis of synthetic cannabinoids and their metabolites in urine or other biological fluids, other analytical methods including nuclear magnetic resonance have been described for their analysis. Review of the literature illustrates the hazards associated with SC use. A range of severe toxicities affecting numerous systems has been identified, such as arrhythmias, myocardial infarction, sudden cardiac death, psychosis, suicidal ideation, seizures, acute tubular necrosis, and intracranial hemorrhage. Additionally, a recent outbreak of coagulopathies and at least 4 associated deaths due to SCs tainted with brodifacoum have been reported.
A literature search was conducted in the PubMed MEDLINE and SciFinder databases. Results in PubMed were limited to human studies, and only English articles were included. No database filters were used for publication dates; however, articles from 2012 to 2018 were selected for this review. MeSH (medical subject headings) terms used in the search were cannabinoids, designer drugs, and street drugs. Keywords used were synthetic marijuana, synthetic cannabinoids, and other related terms. K2 and spice were also used as keywords in the search to include well-known synthetic marijuana brands. Keywords and MeSH terms for bleeding in relation to adverse effects of SCs were also used. Synthetic cannabinoids are laboratory synthesized products eliciting effects way more than their natural counterparts. These compounds are more potent in generating intoxicating effects and are also difficult to be detected in conventional screening tests. Their clinical side effects are also more pronounced than natural cannabinoids, and their antidotes are also not known. However, they are also therapeutically found to be very effective in many health conditions, as these act by interacting with almost ubiquitously distributed cannabinoid receptors (CB1 and CB2) in the human body and by other mechanisms also that do not involve these receptors. All the issues related to their appropriate dosage, mode of action, acute and chronic effects in vivo, interaction with other drugs, their metabolism, etc. need much research to be done so that it will be easier to predict their different aspects in human subjects in more appropriate way. Further, development of strict legislation and regulation is required to be done so that their abuse can be curbed, and toxic effects can be reduced, but medicinal benefits and usage can be enhanced.
A second search of the literature was completed in the SciFinder database. Due to SciFinder’s recommended method of searching, the phrase toxicity of synthetic cannabinoids was used as the main search query to help the database identify the major concepts of toxicity and synthetic cannabinoids. Because SciFinder also searches MEDLINE, results were limited to the CAplus index in SciFinder, which is a comprehensive database of the chemistry literature that includes resources not covered in MEDLINE.
| System | Synthetic Cannabinoid Intoxication Effects |
| Cardiac | Tachycardia, supraventricular tachycardia, ventricular fibrillation, myocardial infarction, sudden cardiac death, coronary arterial thrombosis |
| Hematological | Immune thrombocytopenia, intracranial hemorrhage, coagulopathy |
| Neurological | Dizziness, drowsiness, tremor, altered mental status, seizure, acute ischemic infarction |
| Psychiatric | Agitation, anxiety, paranoia, psychosis, suicidal ideation, delirium, dissociation, depersonalization, hallucinations, disorganized behavior |
| Renal | Acute kidney injury, acute tubular necrosis |
| Other | Nausea, vomiting, rhabdomyolysis, hyperthermia |