Withdrawal: It is unclear as to whether there are any withdrawal symptoms ensuing following discontinuation of chronic CBD oil administration. It is apparent that there are marijuana withdrawal symptoms – it took years for these to receive legitimate scientific attention in the literature.  Though most would speculate that CBD is unlikely to cause discontinuation effects, withdrawal symptoms cannot be ruled out among long-term, chronic users.
Chronic administration: There’s minor evidence suggesting that chronic administration of CBD may be deleterious to neurophysiological health. This evidence didn’t come from a human study, but discovered that chronic CBD administration (10 mg/kg, intraperitoneal injections) for 14 days reduced BDNF expression in various regions of the brain.  It also altered protein expression of TrkB and phospho-ERK1/2 – indicating (potentially) unwanted epigenetic changes.
Dosage: It is relatively difficult to determine the optimal dosage of CBD for anxiety. CBD is thought to have an extremely low bioavailability when administered orally as a standalone agent.  The standard dosage used in research is around 600 mg for anxiolytic effects, but this is in an oral format which has a bioavailability of around 6%.  Perhaps even higher dosages and/or cofactors are necessary to improve oral absorption. (Source: www.mdpi.com/1424-8247/5/5/529/pdf).

5-HT1A partial agonist: Modulation of neurotransmission at the 5-HT1A receptor is understood to provide anxiolytic, antidepressant, and neuroprotective effects.  Research has demonstrated the effect of cannabidiol as a 5-HT1A receptor partial agonist, meaning it binds to the receptor site but only stimulates the receptor partially (relative to a full agonist).  Studies with cloned human cell cultures note that cannabidiol displaces 5-HT1A agonists from 5-HT1A receptor sites in a dose-dependent manner.


THC is the primary psychoactive compound in marijuana and it is what people are searching for when they want a product that gives them a "high." Unlike THC, CBD isn't known to cause psychoactive effects, and is therefore attractive to those who want to avoid the high but who believe there are other benefits of CBD, said Sara Ward, a pharmacologist at Temple University in Philadelphia. [Healing Herb? Marijuana Could Treat These 5 Conditions]

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