Effect of cannabinoids on the activity of monoamine oxidase in normal human platelets

Mazor, Moshe; Dvilansky, A; Aharon, M.; Lazarovitz, Z; Nathan, Ilana

doi:10.3109/13813458209082649

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…One study identified a small dose-dependent activation of phenytoin hydroxylation in human liver microsomes in the presence of THC, 11-OH THC, or THC-COOH; (Bland et al, 2005) In studies of monoamine oxidase (MAO) function: THC isomers and CBD exerted no or minimal impact on platelet MAO activity ex vivo (the greatest inhibitory effect was exerted by Δ 9 -THC, with Ki 7.8 µM); (Mazor et al, 1982) marijuana had no impact on ex vivo platelet MAO function in the four hours following smoking; (Stillman et al, 1978) and THC and CBD exerted little or no inhibition of liver or brain MAO activity in vitro, although some cannabis extract components may inhibit particularly the MAO-B isoform. (Schurr and Rigor, 1984) In long-term cannabis users, cannabis smoking did not affect ex vivo plasma dopamine βhydroxylase activity acutely, and a 3 day abstinence from cannabis was associated with a <10% increase compared to baseline activity.…”

Section: In Vitro and Ex Vivo Datamentioning

confidence: 99%

Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Stout¹,

Cimino²

2013

Drug Metabolism Reviews

300

230

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Exogenous cannabinoids are structurally and pharmacologically diverse compounds that are widely used. The purpose of this systematic review is to summarize the data characterizing the potential for these compounds to act as substrates, inhibitors, or inducers of human drug metabolizing enzymes, with the aim of clarifying the significance of these properties in clinical care and drug interactions. In vitro data were identified that characterize cytochrome P-450 (CYP-450) enzymes as potential significant contributors to the primary metabolism of several exogenous cannabinoids: tetrahydrocannabinol (THC; CYPs 2C9, 3A4); cannabidiol (CBD; CYPs 2C19, 3A4); cannabinol (CBN; CYPs 2C9, 3A4); JWH-018 (CYPs 1A2, 2C9); and AM2201 (CYPs 1A2, 2C9). CYP-450 enzymes may also contribute to the secondary metabolism of THC, and UDP-glucuronosyltransferases have been identified as capable of catalyzing both primary (CBD, CBN) and secondary (THC, JWH-018, JWH-073) cannabinoid metabolism. Clinical pharmacogenetic data further support CYP2C9 as a significant contributor to THC metabolism, and a pharmacokinetic interaction study using ketoconazole with oromucosal cannabis extract further supports CYP3A4 as a significant metabolic pathway for THC and CBD. However, the absence of interaction between CBD from oromucosal cannabis extract with omeprazole suggests a less significant role of CYP2C19 in CBD metabolism. Studies of THC, CBD, and CBN inhibition and induction of major human CYP-450 isoforms generally reflect a low risk of clinically significant drug interactions with most use, but specific human data are lacking. Smoked cannabis herb (marijuana) likely induces CYP1A2 mediated theophylline metabolism, although the role of cannabinoids specifically in eliciting this effect is questionable.

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Section: In Vitro and Ex Vivo Datamentioning

confidence: 99%

Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Stout¹,

Cimino²

2013

Drug Metabolism Reviews

300

230

View full text Add to dashboard Cite

show abstract

“…They catalyze the breakdown of monoamine neurotransmitters, including dopamine, epinephrine, noradrenaline, and serotonin [ 93 , 94 ]. Research on the effects of hashish components on monoamine oxidase concluded that CBD has no effects on the activity of monoamine oxidase in both porcine and human brain tissues [ 93 , 95 ]. However, co-administration of CBD with THC completely diminished the inhibitory effects of THC on monoamine oxidase activity [ 93 ].…”

Section: Cbd and Monoamine Oxidasementioning

confidence: 99%

Regulatory Effects of Cannabidiol on Mitochondrial Functions: A Review

Chan

Duncan

2021

Cells

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Cannabidiol (CBD) is part of a group of phytocannabinoids derived from Cannabissativa. Initial work on CBD presumed the compound was inactive, but it was later found to exhibit antipsychotic, anti-depressive, anxiolytic, and antiepileptic effects. In recent decades, evidence has indicated a role for CBD in the modulation of mitochondrial processes, including respiration and bioenergetics, mitochondrial DNA epigenetics, intrinsic apoptosis, the regulation of mitochondrial and intracellular calcium concentrations, mitochondrial fission, fusion and biogenesis, and mitochondrial ferritin concentration and mitochondrial monoamine oxidase activity regulation. Despite these advances, current data demonstrate contradictory findings with regard to not only the magnitude of effects mediated by CBD, but also to the direction of effects. For example, there are data indicating that CBD treatment can increase, decrease, or have no significant effect on intrinsic apoptosis. Differences between studies in cell type, cell-specific response to CBD, and, in some cases, dose of CBD may help to explain differences in outcomes. Most studies on CBD and mitochondria have utilized treatment concentrations that exceed the highest recorded plasma concentrations in humans, suggesting that future studies should focus on CBD treatments within a range observed in pharmacokinetic studies. This review focuses on understanding the mechanisms of CBD-mediated regulation of mitochondrial functions, with an emphasis on findings in neural cells and tissues and therapeutic relevance based on human pharmacokinetics.

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“…Fisar [16] tested three cannabinoid receptor agonists, anandamide, tetrahydrocannabinol (Δ 9 -THC), and WIN55212-2, for MAO activity in a crude mitochondrial fraction isolated from pig brain cortex and found MAO inhibition only at high concentrations. However, earlier studies found contrary effects of THC on MAO activity: THC elicited inhibitory [24], stimulatory [25], or no pharmacological effects [26], according to the different references.…”

Section: Introductionmentioning

confidence: 99%

Interactions of endocannabinoid virodhamine and related analogs with human monoamine oxidase-A and -B

Pandey

Chaurasiya

Tekwani

et al. 2018

Biochemical Pharmacology

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The endocannabinoid system plays an important role in the pathophysiology of various neurological disorders, such as anxiety, depression, neurodegenerative diseases, and schizophrenia; however, little information is available on the coupling of the endocannabinoid system with the monoaminergic systems in the brain. In the present study, we tested four endocannabinoids and two anandamide analogs for inhibition of recombinant human MAO-A and -B (monoamine oxidase). Virodhamine inhibited both MAO-A and -B (IC values of 38.70 and 0.71 μM, respectively) with ∼55-fold greater inhibition of MAO-B. Two other endocannabinoids (noladin ether and anandamide) also showed good inhibition of MAO-B with IC values of 18.18 and 39.98 μM, respectively. Virodhamine was further evaluated for kinetic characteristics and mechanism of inhibition of human MAO-B. Virodhamine inhibited MAO-B (K value of 0.258 ± 0.037 μM) through a mixed mechanism/irreversible binding and showed a time-dependent irreversible mechanism. Treatment of Neuroscreen-1 (NS-1) cells with virodhamine produced significant inhibition of MAO activity. This observation confirms potential uptake of virodhamine by neuronal cells. A molecular modeling study of virodhamine with MAO-B and its cofactor flavin adenine dinucleotide (FAD) predicted virodhamine's terminal -NH group to be positioned near the N5 position of FAD, but for docking to MAO-A, virodhamine's terminal -NH group was far away (∼6.52 Å) from the N5 position of FAD, and encountered bad contacts with nearby water molecules. This difference could explain virodhamine's higher potency and preference for MAO-B. The binding free energies for the computationally-predicted poses also showed that virodhamine was selective for MAO-B. These findings suggest potential therapeutic applications of virodhamine for the treatment of neurological disorders.

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Effect of cannabinoids on the activity of monoamine oxidase in normal human platelets

Cited by 7 publications

References 22 publications

Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Regulatory Effects of Cannabidiol on Mitochondrial Functions: A Review

Interactions of endocannabinoid virodhamine and related analogs with human monoamine oxidase-A and -B

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