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Neurotoxicity of Exogenous Cannabinoids

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Handbook of Neurotoxicity

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Abstract

The endogenous cannabinoid system regulates diverse aspects of physiological functions via specific cannabinoid receptors (CB) expressed in the brain and periphery. CB1 receptors mediate various neurological processes, whereas CB2 receptors mainly regulate immune responses and are involved in development of drug addiction and neuroinflammation. The cannabinoids are a heterogeneous group of endo-, phyto-, and synthetic cannabinoids. Cannabis and its products have been used for millennia, and these remain the most frequently used substances around the world. Δ9-Tetrahydrocannabinol (Δ9-THC), the main psychoactive constituent of cannabis, produces psychotic-like symptoms. Acute and chronic cannabis use may impair learning and memory, attention, and psychomotor functions; however, studies on the life-lasting effects of cannabis on brain structure are ambiguous. During the last decade, a worrying trend has been observed regarding the increasing popularity of more potent, addictive, and harmful synthetic cannabinoids (SCs). Unlike Δ9-THC, SCs use may lead to severe adverse effects including seizures, agitation, aggression, violence, anxiety, and panic attacks. Acute intoxication may be life-threatening or lead to persistent impairments in emotional and cognitive processing as a result of irreversible brain damage. This chapter describes the current state of knowledge regarding various aspects of the neurotoxicity of exogenous cannabinoids, including the harmful effects of their use during pregnancy.

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Abbreviations

2-AG:

2-Arachidonoylglycerol

AEA:

N-arachidonoylethanolamine

CB1:

Type 1 cannabinoid receptor

CB2:

Type 2 cannabinoid receptor

CBC:

Cannabichromene

CBD:

Cannabidiol

CBG:

Cannabigerol

CBN:

Cannabinol

CPP:

Conditioned place preference

CUD:

Cannabis use disorder

DAG:

Diacylglycerol

DAGLα:

Diacylglycerol lipase-α

EMCDDA:

European Monitoring Centre for Drugs and Drug Addiction

FAAH:

Fatty acid amide hydrolase

IVSA:

Intravenous self-administration

ICSS:

Intracranial self-stimulation

MAGL:

Monoacylglycerol lipase

NPS:

New psychoactive substances

SCs:

Synthetic cannabinoids

UNODC:

United Nations Office on Drugs and Crime

Δ9-THC:

Δ9-Tetrahydrocannabinol

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Acknowledgments

Supported by the Medical University of Lodz, Poland (Grant No 503/3-011-01/503-31-002-19), and Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2017SXEXT5) and Regione Sardegna (RASSR03071), Italy.

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Authors and Affiliations

  1. Department of Pharmacodynamics, Medical University of Lodz, Lodz, Poland

    Jolanta B. Zawilska & Katarzyna Kuczyńska

  2. CNR Institute of Neuroscience, National Research Council, Cagliari, Italy

    Jessica Bratzu & Liana Fattore

Authors
  1. Jolanta B. Zawilska
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  2. Katarzyna Kuczyńska
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  3. Jessica Bratzu
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  4. Liana Fattore
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Correspondence to Jolanta B. Zawilska .

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  1. Department of Biomedical Sciences, Quillen College of Medicine East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Zawilska, J.B., Kuczyńska, K., Bratzu, J., Fattore, L. (2022). Neurotoxicity of Exogenous Cannabinoids. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-031-15080-7_206

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