Cannabidiol Adverse Effects and Toxicity PMC

Following these discoveries, CBD’s effects in animal models of opioids addiction were more thoroughly considered. In morphine-dependent rats, CBD’s impact on THC-induced attenuation of morphine abstinence syndrome was liberty caps identification investigated. Before naloxone administration for the precipitation of acute withdrawal symptoms, rats were pre-treated with either vehicle or CBD (10 mg/kg), accompanied by either THC (2 mg/kg) or vehicle injection.

Are there any side effects or risks to consider when using CBD?

Cognition can be assessed by testing 3-word recall, asking multi-step math problems, or recalling details from a brief fictional story, as demonstrated on the St. Louis University Mental Status Exam. Berl V, Hurd YL, Lipshutz BH, Roggen M, Mathur EJ, Evans M. A randomized, triple-blind, comparator-controlled parallel study investigating the pharmacokinetics of cannabidiol and tetrahydrocannabinol in a novel delivery system, Solutech, in association with cannabis use history. In humans receiving the drug for the treatment of epilepsies and psychiatric disorders, the most common mirtazapine and alcohol AEs included tiredness, diarrhea, nausea, and hepatotoxicity. Overall, the incidence of these occurrences is low and, in comparison with other drugs employed for the treatment of these diseases, CBD has a better side effect profile. Amongst all of these positive developments, unapproved CBD products are being sold across the US and in other countries without rigorous standardization of CBD potency, the content of other constituents, and with unproven claims of health effects. Now that Epidiolex® is approved, it is likely that off-label prescriptions will increase.

CBD Potential Risks and Side Effects

A 2018 study found that CBD helped reduce cravings during withdrawal from tobacco because of its relaxing effect. In June 2018, the Food and Drug Administration (FDA) approved the prescription use of Epidiolex, a purified form of CBD oil, for treating two types of epilepsy. The literature search was conducted in two electronic databases, MEDLINE and PubMed. The search was restricted to English and French-language articles before 2015.

Where does CBD come from?

Craving scores increased during the first two weeks but progressively returned to baseline levels from the third week of treatment (Trigo et al., 2016) (Table 2). Regarding the safety of CBD, Taylor et al., 2018, in phase I, randomized, double-blind, placebo-controlled study, revealed that CBD was commonly well tolerated. Diarrhea, nausea, headache, and drowsiness were the most frequently reported adverse events across all trial arms in subjects taking CBD.

Despite promising evidence presented above from preclinical studies of rodent models, there was no evidence for CBD decreasing craving levels as compared to placebo groups. Thus, CBD was unable to interfere with symptoms of crack-cocaine withdrawal and craving (Meneses-Gaya et al., 2020). Moreover, the risk for cocaine relapse was similar in CBD- and placebo-receiving participants (Mongeau-Pérusse et al., 2021) (Table 2). After examining the acute and long-term effects of cannabis, CUD appears to conform to the general patterns of changes described in the Koob and Volkow model of addiction.

1. These effects may be related, at least in part, with CBD-mediated improvement of withdrawal symptoms and the reduction of alcohol consumption, motivation, and relapse.
2. The achievement of promising results lately has motivated further research to evaluate the potential utility of CBD in the management of OUD.
3. However, the endogenous cannabinoid system may include additional cannabinoid G protein-coupled receptors (GPCR) GPR55, GPR18, and GPR119, transient receptor potential cation channels (TRP) TRPV, TRPA, TRPM, and TRPC and nuclear peroxisome proliferator-activated receptors (PPAR) [5].
4. CB1, CB2, TRPV1, adenosine A2A, PPARγ, ryanodine, and inositol triphosphate (IP3) receptor antagonists did not prevent CBD-induced intracellular Ca2+ increase, suggesting that these receptors did not mediate these CBD actions.

Though it’s often well-tolerated, CBD can cause side effects, such as dry mouth, diarrhea, reduced appetite, drowsiness and fatigue. CBD can also interact with other medications you’re taking, such as blood thinners. Research indicates that CBD is generally well-tolerated up to doses of around 600 mg and as high as 1500 mg.

Another study, conducted in an experimental animal model, evaluated the effects of CBD on the reward-facilitating and brain reward function effect of morphine by using the intracranial self-stimulation (ICss) paradigm in rats. In contrast, higher doses (10–20 mg/kg) increased ICss thresholds, indicating that brain reward function is decreased by acute administration of CBD. ICss thresholds were lowered by morphine but increased by CBD, suggesting that CBD is unlikely to exhibit abuse potential (Katsidoni et al., 2013) (Table 1). Since CBD carries mild side effects in animal preclinical and human studies (Iffland and Grotenhermen, 2017; Taylor et al., 2018), and exhibits no rewarding properties (Babalonis et al., 2017; Parker et al., 2004), it may be introduced as a great therapeutic candidate for drug abuse.

Their findings represent the first clinical trial to focus on the psychological effects of CBG. Patients who are pregnant should be counseled at length on the potential impact of cannabis on the fetus and the pregnancy. Adults should be informed that cannabis and its paraphernalia are best kept in a locked and hidden location to prevent pediatric intoxication. Though medical marijuana is legal in many states, employers may enforce policies. In an online survey of 117 parents who administered a median CBD-enriched cannabis preparation of 4.3 mg/kg/day for a median duration of 6.8 months for treatment of their children’s epilepsy, 59% reported AEs, primarily gastrointestinal disturbances; however, there was no control group [67].

While promising, more research is needed to understand how CBD might be utilized for the treatment of substance use disorders. Evidence suggests that people can develop a tolerance to THC and may experience withdrawal symptoms. Physical dependence on THC is more likely among people silexan vs xanax who use high-THC cannabis strains. While cannabidiol also interacts with the body’s endocannabinoid system, CBD does not have the same intoxicating properties that THC has. Research suggests it has a good safety profile and is well tolerated at doses up to 600mg to 1,500 mg.

The results of this study indicate that CBD (one dose of 5 mg/kg or 5 mg/kg once daily for 3 days) specifically inhibited conditioned cue-induced heroin-seeking behavior for up to 2 weeks following the last administration without affecting motor function. On the other hand, CBD failed to influence drug-seeking behavior initiated by heroine prime. Moreover, neither the maintenance nor the extinction phase of SA was modified by CBD.

The latter data supports the addictive model of cannabis as insula activation may serve as a biomarker to help predict relapse (Filbey et al. 2016). This brain region contributes to interoceptive awareness of negative emotional states and is differentially activated during craving (Koob and Volkow 2016). This is also consistent with prior findings that the dopaminergic reward system is reactivated during acute craving episodes (Volkow et al. 1999b, 2005; Koob and Volkow 2016). Moreover, in cannabis abusers, but not in controls, acute THC intoxication elicited activation of brain reward regions as assessed by increases in brain glucose metabolism in striatum and orbitofrontal cortex (Volkow et al. 1996a).