CBD appears to have anxiolytic effects in animal models; however, oral doses of 150, 300 or 600 mg CBD did not significantly reduce self-reported anxiety related to experimentally induced stress in healthy participants (n = 61) participating in a neuroimaging study.
Preclinical evidence has demonstrated that pure CBD inhibits several CYP P450 enzymes that play a major role in drug interactions, leading to potential drug-drug interactions that are being investigated clinically with patients taking specific medications.
1. Anti-Inflammatory Effects
CBD acts as an effective inhibitor of leukotriene production by the innate immune system, which inhibits pro-inflammatory compounds while simultaneously increasing production of anti-inflammatory specialised pro-resolving mediators (SPM) from these cells [70].
CBD shows promising analgesic properties when administered to rodent models of neuropathic pain, and this analgesic effect may be enhanced further with opioid medications. A small trial using topical CBD oil on arthritis participants reported an alleviation in symptoms.
CBD has been shown to activate vanilloid receptors (TRPA1, TRPA2) while antagonising TRPM8 receptors – calcium channels which regulate inflammation through TRP receptors. Furthermore, preclinical studies indicate it inhibits pro-inflammatory cytokines and reduces pro-inflammatory metabolites.
2. Anti-Psychotic Effects
CBD has been shown to normalise disconnection between several brain regions that become disconnected in people with psychotic disorders, including the default mode network – active when you focus your attention inward and thus implicated in delusions and hallucinations.
CBD can also help ease anxiety, improve sleep quality and decrease stress – all factors linked to impaired cognition. Research has also indicated that CBD increases hippocampal cell densities and BDNF levels directly, suggesting it could have direct influence over memory function.
Recent RCT results of 88 moderately to severely ill people with schizophrenia demonstrated that six weeks of treatment with CBD plus antipsychotic medication led to significant improvements in symptoms, cognitive performance and global clinical impressions more so than placebo. Notably, this improvement coincided with changes in fMRI brain activity showing decreased activation of the amygdala and anterior cingulate cortex during fearful face processing.
3. Anti-Anxiety Effects
Preclinical and clinical CBD research suggests that it has potency anxiolytic properties. CBD reduces experimentally induced anxiety without inducing sedation or impairing cognition; furthermore, its minimal anxiogenic effects and absence of dependence on CB1Rs make it an attractive solution.
CBD’s anxiolytic effects are exerted through multiple receptor mechanisms and brain regions. One study, performed on subjects in the midbrain dorsal periaqueductal gray region – essential for mediating autonomic responses to fear and anxiety – demonstrated how CBD reduced stress-induced increases in heart rate via 5-HT1AR activation, while in bed nucleus of stria terminalis (BNST), essential for coordinated sustained fear responses, it reduced long-term anxiogenic effects of predator stress by activation of 5-HT1AR activation.
CBD has also been shown to facilitate extinction learning and prevent reconsolidation of conditioned fear, while decreasing reactivity to threat stimuli by altering prefrontal cortical connectivity – but more research needs to be conducted into effective dosing strategies for clinical populations.
4. Anti-Seizure Effects
CBD acts as an effective antiseizure agent in human epileptic patients with drug resistant frontal lobe seizures. A placebo-controlled adjunctive treatment trial demonstrated CBD’s efficacy by significantly reducing seizure frequency and severity (Chalfont Seizure Severity Score) at 4-week and 8-week time points compared with placebo as well as in combination with antiseizure medications such as Clobazam, Droxidopam, Eslicarbazepine Topiramate Zonisamide Warfarin.
CBD has demonstrated direct antiepileptic effects in animal models by decreasing LFP burst amplitude in both Mg2+-free and 4-AP induced epileptiform activity as well as cortical ERK activity. CBD appears to bind strongly to 5-HT1A receptors but doesn’t appear to act as a full agonist, instead exerting its effects through allosteric manipulation of intracellular signaling pathways. Reduced limbic evoked responses in fearful subjects and enhanced consolidation of extinction learning are associated with neuroimaging changes in memory processing regions [108]. Further preclinical research is necessary to ascertain whether synthetic molecules containing standard concentrations of CBD exhibit similar antiepileptogenic and anticonvulsant effects.
5. Pain Relief
CBD interacts with numerous receptors in both the brain and body, yet its main pain relief effect comes through modulation of the endocannabinoid system (ECS). This complex process influences multiple molecular targets simultaneously.
Animal studies have demonstrated the efficacy of CBD topically applied directly to painful joints for pain reduction with no side effects, while oral CBD significantly reduced opiate-induced hyperalgesia in mice.
CBD may help relieve neuropathic pain caused by nerve damage. Its analgesic properties are dose-dependent and have been demonstrated in several animal models of disease; for instance, CBD was shown to decrease surgery-induced mechanical allodynia in mouse models as well as reduce paclitaxel-induced neuropathy in rats; furthermore it enhanced morphine-induced antinociception and enhanced antinociception for pain models like rats; additionally it may improve sleep quality which in turn may relieve some aspects of neuropathic pain indirectly.
