Inhibition of monoamine oxidase activity by cannabinoids
18 Apr 2010-Naunyn-schmiedebergs Archives of Pharmacology (Springer-Verlag)-Vol. 381, Iss: 6, pp 563-572
TL;DR: Investigation of in vitro effects of cannabinoids on the activity of monoamine oxidase found decrease of MAO activity may play a role in some effects of cannabinoid on serotonergic, noradrenergic, and dopaminergic neurotransmission.
Abstract: Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and psychotropic drugs, including cannabinoids. This study investigated in vitro effects of cannabinoids on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters and affecting brain development and function. The effects of the phytocannabinoid Δ9-tetrahydrocannabinol (THC), the endocannabinoid anandamide (N-arachidonoylethanolamide [AEA]), and the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) on the activity of MAO were measured in a crude mitochondrial fraction isolated from pig brain cortex. Monoamine oxidase activity was inhibited by the cannabinoids; however, higher half maximal inhibitory concentrations (IC50) of cannabinoids were required compared to the known MAO inhibitor iproniazid. The IC50 was 24.7 μmol/l for THC, 751 μmol/l for AEA, and 17.9 μmol/l for WIN when serotonin was used as substrate (MAO-A), and 22.6 μmol/l for THC, 1,668 μmol/l for AEA, and 21.2 μmol/l for WIN when phenylethylamine was used as substrate (MAO-B). The inhibition of MAOs by THC was noncompetitive. N-Arachidonoylethanolamide was a competitive inhibitor of MAO-A and a noncompetitive inhibitor of MAO-B. WIN was a noncompetitive inhibitor of MAO-A and an uncompetitive inhibitor of MAO-B. Monoamine oxidase activity is affected by cannabinoids at relatively high drug concentrations, and this effect is inhibitory. Decrease of MAO activity may play a role in some effects of cannabinoids on serotonergic, noradrenergic, and dopaminergic neurotransmission.
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TL;DR: A review of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances is provided in this paper.
Abstract: “K2” and “Spice” drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as “legal highs”. These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate “not for human consumption”, the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications.
437 citations
Cites background from "Inhibition of monoamine oxidase act..."
...However, the prevalent abuse of ∆9-THC and the lack of significant toxicity resulting from MAO inhibition with cannabis indicates this mechanism is unlikely to cause adverse effects reported with Spice use....
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...Furthermore, high doses of THC and other cannabinoids are inhibitors of monoamine oxidase (MAO) (Fišar, 2010, 2012)....
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TL;DR: The background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures are discussed.
Abstract: Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called “bath salts,” have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as “legal ketamine.” Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as “legal Ecstasy.” These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.
324 citations
TL;DR: This review article aims to describe and critically discuss the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one Δ(9)-tetrahydrocannabinol, and the adaptive pro-homeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs.
Abstract: Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant c...
307 citations
Additional excerpts
...7 M) (265); cytochrome P-450 enzymes CYP1A1, CYP1A2, CYP2B6, and CYP2C9 (825); and Mg(2) -ATPase (677)....
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TL;DR: In this article, the authors provide psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of synthetic cannabinoids, including dopamine, CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors.
260 citations
Cites background from "Inhibition of monoamine oxidase act..."
...In addition to this, some SCs show further pharmacodynamic actions (24) which may per se be a reason of clinical concern, such as N-methyl-D-aspartate (NMDA) receptor antagonism (25) and/or monoamine oxidase (MAO) inhibitory properties (26)....
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TL;DR: This review focuses on the latest evidence of psychotic symptoms induced by ingestion of products containing SCs, and reports suggesting that SCs may either exacerbate previously stable psychotic symptoms or trigger new-onset psychosis in individuals with no previous history of psychosis.
129 citations
References
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2,619 citations
"Inhibition of monoamine oxidase act..." refers background in this paper
...Cannabinoids form a group of substances originally found in the cannabis plant, but the term cannabinoid refers to any substance that is specifically recognized by the endocannabinoid system in the body (Howlett et al. 2002; Lambert and Fowler 2005)....
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