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Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ(9)-THC: mechanism underlying greater toxicity?
- Source :
-
Life sciences [Life Sci] 2014 Feb 27; Vol. 97 (1), pp. 45-54. Date of Electronic Publication: 2013 Sep 29. - Publication Year :
- 2014
-
Abstract
- K2 or Spice products are emerging drugs of abuse that contain synthetic cannabinoids (SCBs). Although assumed by many teens and first time drug users to be a "safe" and "legal" alternative to marijuana, many recent reports indicate that SCBs present in K2 produce toxicity not associated with the primary psychoactive component of marijuana, ∆(9)-tetrahydrocannabinol (Δ(9)-THC). This mini-review will summarize recent evidence that use of K2 products poses greater health risks relative to marijuana, and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ(9)-THC may contribute to the observed toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ(9)-THC typically observed in vitro, SCBs in K2 products act as full cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) agonists in both cellular assays and animal studies. Furthermore, unlike Δ(9)-THC metabolism, several SCB metabolites retain high affinity for, and exhibit a range of intrinsic activities at, CB1 and CB2Rs. Finally, several reports indicate that although quasi-legal SCBs initially evaded detection and legal consequences, these presumed "advantages" have been limited by new legislation and development of product and human testing capabilities. Collectively, evidence reported in this mini-review suggests that K2 products are neither safe nor legal alternatives to marijuana. Instead, enhanced toxicity of K2 products relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2Rs, highlights the inherent danger that may accompany use of these substances.<br /> (© 2013.)
- Subjects :
- Animals
Cannabinoid Receptor Agonists metabolism
Cannabinoid Receptor Agonists pharmacology
Cannabinoid Receptor Agonists toxicity
Cannabinoids metabolism
Cannabinoids toxicity
Designer Drugs metabolism
Designer Drugs toxicity
Dronabinol metabolism
Dronabinol toxicity
Humans
Illicit Drugs metabolism
Illicit Drugs pharmacology
Illicit Drugs toxicity
Receptor, Cannabinoid, CB1 agonists
Receptor, Cannabinoid, CB1 metabolism
Receptor, Cannabinoid, CB2 agonists
Receptor, Cannabinoid, CB2 metabolism
Cannabinoids pharmacology
Designer Drugs pharmacology
Dronabinol pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 97
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 24084047
- Full Text :
- https://doi.org/10.1016/j.lfs.2013.09.017