Another model for BD and schizophrenia is PPI of the startle reflex both in humans and animals, which is disrupted in these diseases. Peres et al., list five animal studies, where mostly 30 mg/kg CBD was administered and had a positive effect on PPI.20 Nonetheless, some inconsistencies in explaining CBD effects on PPI as model for BD exist. For example, CBD sometimes did not alter MK-801-induced PPI disruption, but disrupted PPI on its own.20 If this effect can be observed in future experiments, it could be considered to be a possible side effect. Because CBD might slow how your body breaks down these drugs, that could mean higher levels of the drug in your body, and even cause more side effects. CBD may also change how other medicines work because they are broken down by the liver. So far, the FDA has approved only one CBD medication, called Epidiolex, for the treatment of two types of epilepsy.

Update on Cannabidiol Clinical Toxicity and Adverse Effects: A Systematic Review

Following 90 days of oral CBD ( mg/kg/day), liver and kidney weights in rhesus monkeys were 13-56% greater than controls, without morphological changes in the organs [61]. CBD’s neuroprotective effect was investigated in human neuroblastoma SH-SY5Y cells during and after neuronal differentiation [60]. Terminally-differentiated cells incubated with 2.5 µM CBD were not protected against ROS produced by exposure to glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide.

6. Respiratory Effects

Despite known toxicity and increased availability of marijuana, many people continue to abuse synthetic cannabinoids for various reasons including lower cost as compared to marijuana and lack of detection on routine drug screening. CBD’s interaction with CYP enzymes can reduce or potentiate the effects of other drugs [19, 22, 80]. In 1974, Karniol et al. investigated effects of oral 0, 15, 30, and 60 mg CBD alone, 0 and 30 mg THC alone, and CBD and THC combinations to study potential drug-drug interactions in a double-blind trial in 40 healthy male volunteers [81].

Endocrine effects and glycemic (including appetite) effects

5-HT1A receptor activation is also involved in CBD neuroprotection in in vitro adult and rat newborn models of the acute hypoxic-ischemic brain [18]. Marijuana is the most widely used illicit drug in Australia, most people have a pleasant experience with the psychoactive drug. Cannabinoids can have adverse effects particularly in children if high doses are consumed which result in CNS depression and a coma lasting up to 36 hours. With chronic heavy smoking, users experience increased cough, sputum production, and wheezing.

Risk of bias

Synthetic cannabinoids are the most abused synthetic drug and second most abused drug among adolescents. [7]Reports of abuse and toxicity are steadily growing, as the number of synthetic cannabinoids produced is cannabidiol addictive increases. Increasing varieties of synthetic cannabinoids have been synthesized over the last ten years to avoid classification as illegal agents by making chemical modifications to compounds.

The trial consisted of subjects being administered oral CBD 200 mg daily for 3 days. This resulted in common AEs, varying between groups with mild and moderate hepatic impairment. The subject group with mild hepatic impairment had one case of diarrhea and dizziness, while the subject group with moderate hepatic impairment had one case of diarrhea and a low platelet count. However, there was no case of AEs in the subject group of severe hepatic impairment.

Cannabis and Public Health

• In adults with chronic pain, patients treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms [24].
• In a retrospective study of 74 patients, age range 1-18 years, CBD dosage ranged from 1 to 20 mg/kg/day for more than 3 months (average 6 months), 47% AEs were reported, prominently [69].
• Subjects were taking concomitant medication such as paracetamol, acetaminophen, and dipyrone.

This is demonstrated by the increased rates of adverse events, serious adverse events and withdrawals in trials for childhood epilepsy syndromes but not other indications. Additional safety data from clinical trials outside of childhood epilepsy syndromes and from studies of OTC CBD products would be beneficial. Strengths of the present study include its pre-registered protocol, comprehensive systematic search strategy, and its timeliness as the first meta-analysis of the safety and tolerability of CBD across all indications. The overall quality of studies included was high and it is unlikely that a significant amount of bias was introduced.

Neurological and neurospychiatric effects

The CB1 receptors are predominantly located in the brain, with a wide distribution. The highest densities are found in the frontal cerebral cortex (higher functioning), hippocampus (memory, cognition), basal ganglion and cerebellum (movement), and striatum (brain reward). Other brain regions in which the CB1 receptors are found include areas responsible for anxiety, pain, sensory perception, motor coordination, and endocrine function.

As such, the effects of synthetic cannabinoids can be much more potent than THC thus increasing the effects seen physiologically and toxicologically. Cannabinoid intoxication occurs most frequently through inhalation, whether being used recreationally or medicinally. 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.

• Breathalyzer tests have also been proposed, but since small amounts of cannabis continue to be released from fat into the blood long after short-term impairment wears off, this method has not been promoted.
• CBD was also shown to interact with P-glycoprotein efflux transporters involved in multidrug resistance [111] and may also affect placental permeability and pharmacokinetics of other drugs.
• There are many CBD products on the market – everything from gummies to oils to sprays – and you should know the risks before you decide to try it.