An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies PMC

Contains more than 100 phytocannabinoids that can interact with cannabinoid receptors CB1 and CB2. None of the cannabinoid receptor ligands is entirely CB1- or CB2-specific. The effects of cannabinoids therefore differ not just because of different potency at cannabinoid receptors but also because they can interact with other non-CB1 and non-CB2 targets, such as TRPV1, GPR55, and GPR119. THC is a partial agonist at both cannabinoid receptors, but its psychotomimetic effect is produced primarily via activation of the CB1 receptor, which is strongly expressed in the central nervous system, with the noteworthy exception of the brain stem.

The separation was isocratic with 25 % water (0.1 % formic acid) and 75 % acetonitrile (0.1 % formic acid) and a flow of 0.3 mL/min. In case of QTOF with 35 % water (0.1 % formic acid) and 65 % acetonitrile (0.1 % formic acid) and a flow of 0.45 mL/min. The evaluation took place after fragmentation of the mother ion into three mass traces for each compound. As quantifier for ∆
9-THC and CBD, the mass transition m/z 315 to 193 was used. In case of QTOF, quantification was conducted over accurate mass and control of fragmentation pattern.

Toxicological Properties of Δ9-tetrahydrocannabinol and Cannabidiol

Systematically recorded data were extracted from studies that had been published in a peer-reviewed journal or reported on; data from posters, abstracts and other informal reports that had not been subject to peer review were excluded. If a study reported both treatment-related adverse events and adverse events we preferentially extracted adverse events, to reduce the risk of unanticipated adverse events being inadvertently disregarded. If two or more reports of the same study contained conflicting data, we preferentially used the data reported on

  • Children who have more serious symptoms or those with serious side effects may need to stay in the hospital for treatment.
  • Effort is made to ensure that the information contained in this monograph is accurate at the time it was published.
  • More than 400 active compounds have been isolated from the cannabis plant.
  • Leweke et al. noted that CBD moderately inhibits degradation of the endocannabinoid anandamide [38].
  • Administering 10 mg/kg oral CBD to humans leads to blood levels of 0.01 μg/ml.6 This corresponds to human blood levels of 0.12 μg/ml, when 120 mg/kg CBD was given to humans.

Commercial CBD products are usually crude extracts from whole hemp plants (i.e., including flowers and stems). In other ways (e.g., in extracting the food-approved plant parts such as seeds), contents in the range of 1–10% CBD, which are typically advertised, cannot be achieved. No further specific enrichment or purification of CBD is often conducted, so that the commercial extracts are regularly a cannabinoid mixture rather than pure CBD. Otherwise, extracts may be cleaned with different processes such as winterization, or partial fractionation using supercritical CO

3. Hepatic Effects

You have a higher risk of developing CHS if you use cannabis at least once a week. Your risk also increases if you have used cannabis since adolescence. Generally, these products pose a risk to human health considering EFSA’s ARfD that is is cannabidiol addictive considerably exceeded, even without consideration of THCA. The ∆
9-THC dose leading to intoxication is considered to be in the range of 10 to 20 mg (very high dose in heavy episodic cannabis users up to 60 mg) for cannabis smoking


  • CBD treatment significantly increased serum anandamide concentrations.
  • A 104-week oral carcinogenicity study in Wistar rats (referred to in 56) revealed no drug-related neoplastic findings.
  • You have a higher risk of developing CHS if you use cannabis at least once a week.
  • This has been well documented throughout the recent legalization of recreational marijuana in Colorado, and now other states.

Cannabinoid toxicity usually occurs due to overuse and abuse or inadvertant ingestions of cannabis. Accidepntal overuse can occur with marijuana edibles due to excessive ingestion during the extended, unanticipated time it can take for peak action. [6]Inadvertant ingestions most often occur in the pediatric population due to exploratory behavior and ingesting what may otherwise look like a normal food product. Greater availability due to legalization and commercial availability has led to novel preparations of cannabis, including baked goods, various candies, hash, and oils.

Side Effects

Claims of “THC-free”, used by most manufacturers, even on highly contaminated products – sometimes based on the use of unsuitable analytical methodologies with limits of detection in the percentage range –, have to be treated as fraudulent or deceptive food information. Some, partly older,
in vitro studies put up hypotheses about the conversion of CBD to ∆
9-THC under acidic conditions such as in artificial gastric juice

. If these proposals could be confirmed with
in vivo data, consumers taking CBD orally could be exposed to such high ∆
9-THC levels that the threshold for pharmacological action could be exceeded

. However, taking a closer look at these
in vitro studies raises some doubts. If CBD was to be converted to ∆
in vivo, typical ∆
9-THC metabolites should be detectable in blood and urine, but this has not been observed in oral or inhalatory CBD studies


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