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As the use of CBD increases steadily, there have been many concerns about the efficacy and safety profile of this compound in humans. Early studies investigating the physiological effects of CBD in healthy human subjects have provided evidence suggesting that CBD is not risk-free. At different concentrations of use, these studies have shown that CBD also presents with different adverse effects, just as other natural products and synthetic drugs. This explains why CBD use in modern medicine has been confined to the adjunctive treatment of chronic and rare diseases with standard treatment modalities.
Adverse effects of cannabidiol
Cannabidiol is a useful natural product which, like others, can also be harmful. Studies have suggested that the common adverse effects of CBD are concentration-dependent. There are also different hypotheses explaining why CBD can be toxic in humans. Some experts have argued the possibility of CBD’s metabolic conversion to tetrahydrocannabinol—a psychoactive compound with known adverse effects. There are also other arguments proposing that the adverse effects experienced after using a CBD-derived product are caused by residual THC contaminants in these products. The most commonly reported adverse effects of CBD include:
Neurological side effects
Neurological side effects of cannabidiol were first reported in long-term uses of the CBD-derived products. Just like full-spectrum cannabis extracts, there are studies suggesting that the use of cannabis for an extended period of time causes cognitive impairment, memory loss, and a few neurobehavioral disorders. In 2010, a research report investigating the effects of cannabinol in oligodendrocytes was published by Glia. Using Sprague Dawley rats, the researchers concluded that CBD induces a concentration-dependent decrease in the viability of these brain cells. This finding supports earlier suggestions that CBD can induce brain cell death. There are also many animal studies reporting that a high concentration of CBD can cause tremor and CNS inhibition.
Hepatic side effects
Cannabidiol has long been known to activate the hepatic enzymes responsible for the metabolism of drugs. CBD acts as a competitive inhibitor; these liver enzymes and significantly reduce their physiological capability to metabolize drugs. This observation has fuelled various research studies investigating how CBD-induced microsome inactivation can cause adverse effects in the liver. Unlike other adverse effects of CBD, the hepatic side effects were only noticed during clinical trials and studies.
Abnormal liver function test values were noticed in patients using CBD products as a regular regimen. In 2016, The Lancet Neurology published the report of an open-label interventional trial on the efficacy of CBD in the management of epilepsy. About 12% of the participants in this study showed elevated liver function tests. As regards hepatic health, the most common adverse effect on CBD includes liver injury, elevated aspartate aminotransferase, elevated alanine aminotransferase, and chronic cholecystitis.
Gastrointestinal adverse effects
Gastrointestinal side effects are the most commonly reported adverse effects of CBD, especially in first-time users. The fact that these effects are more pronounced in children explains why approved CBD-derived drugs are only licensed for use in children older than two years. The New England Journal of Medicine published the details of research examining the effect of cannabidiol on drop-seizures in the Lennox-Gastaut Syndrome. Unexpectedly, a range of serious gastrointestinal adverse effects was noticed in the participants. Currently, the documented gastrointestinal adverse effects of CBD include diarrhea, weight loss, nausea, loss of appetite, constipation, and abdominal pain.
Cardiovascular adverse effects
The cardiovascular side effects of CBD are considered to be an extension of its physiological effects on the cardiovascular system. Although there are many reviews and reports on this subject, the side effects reported so far are not well-defined. Animal studies have suggested that the cardiovascular side effects of CBD significantly depend on serum CBD concentration. An earlier study on the toxicity of cannabinoids in rhesus monkeys provided the first report of CBD-induced cardiovascular abnormalities. CBD’s dose-dependent side effects on the cardiovascular system include bradycardia, cardiac failure, hypopnea, and severe hypotension.
Reproductive adverse effects
Reports of CBD-induced hormonal imbalance in women of reproductive age is increasing steadily. Natural products scientists have attempted to study the risk factors and the physiological mechanism connected with these observations. Based on currently available consumer reports, the adverse reproductive effects caused by CBD include inhibition of progesterone, estradiol, and testosterone. In many animal studies, it has also been observed that CBD can cause developmental toxicity and increased fetal mortality.
The range of side effects currently reported by different CBD users are many and are yet to be well documented. It is recommended that CBD and other cannabis-derived products should only be used under expert medical supervision.