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Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans

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Abstract

Background

Acute and chronic exposure to cannabinoids has been associated with cognitive deficits, a higher risk for schizophrenia and other drug abuse. However, the precise mechanism underlying such effects is not known. Preclinical studies suggest that cannabinoids modulate brain-derived neurotrophic factor (BDNF). Accordingly, we hypothesized that Δ9-tetrahydrocannabinol (Δ9-THC), the principal active component of cannabis, would alter BDNF levels in humans.

Materials and methods

Healthy control subjects (n = 14) and light users of cannabis (n = 9) received intravenous administration of (0.0286 mg/kg) Δ9-THC in a double-blind, fixed order, placebo-controlled, laboratory study. Serum sampled at baseline, after placebo administration, and after Δ9-THC administration was assayed for BDNF using ELISA.

Results

Δ9-THC increased serum BDNF levels in healthy controls but not light users of cannabis. Further, light users of cannabis had lower basal BDNF levels. Δ9-THC produced psychotomimetic effects, perceptual alterations, and “high” and spatial memory impairments.

Implications

The effects of socially relevant doses of cannabinoids on BDNF suggest a possible mechanism underlying the consequences of exposure to cannabis. This may be of particular importance for the developing brain and also in disorders believed to involve altered neurodevelopment such as schizophrenia. Larger studies to investigate the effects of cannabinoids on BDNF and other neurotrophins are warranted.

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Abbreviations

Δ-9-THC:

delta-9-tetrahydrocannabinol

CB:

Cannabinoid

BDNF:

brain derived neurotrophic factor

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Acknowledgements

The authors acknowledge the critical clinical research contributions of the Biological Studies Unit, VA Connecticut Healthcare System, including Brenda Breault RN, BSN; Elizabeth O’Donnell, RN; Angelina Genovese, RNC, MBA; Sonah Yoo, RPh; Robert Sturwold, RPh; and Mr. Willie Ford. This study was supported by the National Institute of Drug Abuse (DA12382-01 and DA020750 to DCD) and National Institute on Alcohol Abuse and Alcoholism (AA16311 and to DCD). In addition, the authors acknowledge support from the Department of Veterans Affairs Schizophrenia Biological Research Center. A.S. was supported in part by CTSA grant #KL RR024138 from the National Institute of Research Resources, a component of the National Institute of Health (NIH) and the NIH Roadmap for Medical Research.

Declaration of interest

There are no direct or indirect conflicts of interest for any of the authors relevant to the subject of this manuscript.

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Authors and Affiliations

  1. Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT, USA

    Deepak Cyril D’Souza & Edward Perry

  2. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA

    Deepak Cyril D’Souza, Brian Pittman & Edward Perry

  3. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Deepak Cyril D’Souza, Brian Pittman, Edward Perry & Arthur Simen

  4. Psychiatry Service, 116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA

    Deepak Cyril D’Souza

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  1. Deepak Cyril D’Souza
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Correspondence to Deepak Cyril D’Souza.

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D’Souza, D.C., Pittman, B., Perry, E. et al. Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology 202, 569–578 (2009). https://doi.org/10.1007/s00213-008-1333-2

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