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Search Completed | Title | Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent
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Current Drug Safety, 2011, 6, 000-000 1
Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent
Mateus Machado Bergamaschi1,2, Regina Helena Costa Queiroz1, José Alexandre S. Crippa*,2 and Antonio Waldo Zuardi2
1Department of Clinical, Toxicological and Food Sciences Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, SP, Brazil
2Department of Neuroscience and Behavior, School of Medicine, University of São Paulo and National Institute of Translational Medicine (INCT-TM, CNPq) Ribeirão Preto, São Paulo, Brazil
Abstract: Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were “cannabinoids”, “cannabidiol” and “side effects”. Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.
Keywords: Cannabidiol, cannabinoid, cannabis sativa, CBD, marijuana, safety, side effects, toxicity.
Cannabidiol (CBD) is a component of Cannabis sativa and constitutes up to 40% of the extracts of the plant . However, CBD concentrations are highly variable and depend on the growing conditions, the different phenotypes of illicit cannabis, and on the part of the plant analyzed . Evidence suggests that the potency of CBD has decreased in recent years, while THC concentrations have increased, since
CBD induces markedly different psychological effects compared to the best known marijuana compound, 9- tetrahydrocannabinol (THC) . Despite presenting low affinity for CB1 and CB2 receptors, CBD can still interact with these receptors at doses equal to or lower than 1 μM. Therefore, there is no certainty about whether this antagonism is non-competitive. CBD can also act as a CB1 receptor inverse agonist at concentrations below those needed to bind to the CB1 orthosteric site. Moreover, CBD can antagonize THC effects via non-CB1/CB2 receptors, such as GPR55, which is activated by THC and blocked by CBD . The time between the intake of CBD and THC, as well as the CBD/THC ratio, seem to play an important role
*Address correspondence to this author at the Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Hospital das Clínicas - Terceiro Andar, Av. Bandeirantes, 3900, Ribeirão Preto, ZIP Code: 14049-900, São Paulo, Brazil; Tel: +55 16 36022703; Fax: +55 16 36020713; E-mail: email@example.com
in the interaction between these two cannabinoids. CBD can increase the potency of THC by pharmacokinetic interaction if CBD is administrated before THC, or a pharmacodynamic interaction may occur when both cannabinoids are taken together, mainly at a high dose ratio of CBD/THC .
CBD was first isolated by Adams et al. in 1940 , and its structure was identified 23 years later . Since then, a considerable number of published articles have dealt with its chemistry, biochemistry, pharmacology and clinical effects.
antiepileptic, sedative, anxiolytic and antipsychotic activities . The last decade has shown a notable increase in scientific literature on CBD, owing to the identification of its anti-inflammatory and neuroprotective effects. These studies have raised the possibility of therapeutic effects of CBD for diverse conditions, including dementias, cerebral ischemia, diabetes, inflammatory diseases, nausea and psychiatric disorders .
1 and CB2 receptors, CBD is capable of antagonizing CB1 / CB2 receptor agonists at reasonably low concentrations. At CB2 receptors, CBD acts as an inverse agonist. Other mechanisms of action include antagonism of the recently discovered GPR55 receptor; transient receptor potential vanilloid type 1 (TRPV1) agonism; transient receptor potential vanilloid type 2 (TRPV2) agonism; 5- HT1A agonism; antagonism of the putative abnormal-CBD receptor; and regulation of intracellular [Ca2+] .
the use of varieties such as sensimillia
(‘skunk’), provided by
ilegal cannabis growers
dominates the supply of cannabis in many countries
By the year 2000, the primary research topics regarding possible therapeutic effects of CBD were related to its
© 2011 Bentham Science Publishers
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