The Impact of Cannabidiol on Psychiatric and Medical Conditions

Thersilla Oberbarnscheidt, Norman S. Miller

Journal of Clinical and Medical Research, 2020, 12, (7), 393-403.

Doi : 10.14740/jocmr4159

 

Abstract

Cannabidiol (CBD) is a substance chemically derived from Cannabis sativa and discussed to be non-psychoactive. According to the FDA, marijuana is classified as a schedule I substance; however, hemp which is defined as extracts from marijuana including cannabinoids containing less than 0.3% tetrahydrocannabinol (THC), is excluded from that controlled substance act and available at local convenience stores in the US as it is seen as an herbal supplement. CBD is purported to be used for various medical and psychiatric conditions: depression, anxiety, post-traumatic stress disorder, Alzheimer’s or other cognitive illnesses as well as pain. There is also a new trend to use CBD for the
treatment of opioid use disorder. The one CBD product on the market that is FDA approved for the treatment of childhood epilepsy forms Dravet and Lennox-Gastaut syndromes is available under the name Epidiolex. There is a significant difference between this medication and the over-the-counter CBD products that contain very inconsistent strengths of CBD, if they contain it at all, and vary in percentage even from sample to sample. Frequently the so-called CBD products are not containing any CBD at all, but mostly containing THC. This article is a systematic review of literature reviewing the available clinical data on CBD, for use in various medical and psychiatric conditions with focus on a review of the pharmacology and toxicity. Resources used were ORVID, PubMed, MEDLINE, PsychINFO, EMBASE with keywords CBD, cannabidiol, hemp and cannabinoids.

Keywords : Cannabidiol; THC; Cannabis sativa

 

Introduction

CBD, also called cannabidiol, is chemically derived from hemp (Cannabis sativa), which is the most commonly used illicit drug both nationally and internationally [1].

It was first obtained from American hemp and Egyptian hashish in 1940 [2]. In its natural form cannabis consists of the two most well-known active chemicals tetrahydrocannabinol (THC) and CBD as well as about 480 other active cannabinoids (CBs) that are not yet well researched. The THC in the cannabis is the psychoactive ingredient with toxicity. The THC content in a product labeled as CBD is supposed to contain less than 0.3% dry weight of THC in its leaves and buds [3].

Even though CBD use is a global problem, this article will focus on the current situation and trend within the US. Marijuana as well as CBD is purported for use in the US for the self-treatment of numerous medical and psychiatric conditions as a so-called “medicine”. It is commonly used for depression, anxiety, seizures, nausea, appetite enhancer, anti-inflammatory, pain or the new trend to self-treat opioid use disorder [4].

Against the usual course of a medication development, both substances have not been scientifically investigated or developed prior to their use, but were determined by claims in the general public of their medicinal value [5]. Possible toxic effects and drug-drug interactions should be considered, and consumers should be educated about the risks and safety concerns regarding this substance, which are currently not publicized.

Due to CBD being exempt from federal regulations by the in 2018 passed US farm bill, it is easily accessible and available at convenience stores throughout the US [6].

The sale and marketing of CBD and CBD-containing products are very important economic factors as sales reached $2 billion US dollars in 2018 and are rising [7].

Of the US population, 9% of the people less than 35 years of age reported the use of CBD at least once, 6.4% of the people between 45 and 55 years and 3.7% of the people over 55 years of age [8].

The question for public health is if CBD is really non-psychoactive and as safe as it is advertised in the general-public?

Pharmacological Action of CBD

CBD can be ingested in various routes. It is available in the form of oils, lotions, edibles, teas or smoked (Figs. 1, 2) [9]. It is rarely administered intravenously but that route is possible [10].

CBD undergoes a significant first pass metabolism in the liver after ingestion. The bioavailability after oral consumption is estimated 6%, and after smoking is estimated to be about 6-31% [11].

CBD’s primary active metabolite is 7-hydroxy-CBD (7-OH-CBD) [12]. The half-life of CBD depends on the route of administration. Smoked, the half-life is about 27 – 35 h, after oral ingestion 2 – 5 days and the shortest after intravenous injection with about 18 – 33 h [13].

CBD is very lipophilic, similar to cannabis, and easily passes the blood-brain barrier. It gets quickly distributed into adipose tissue and other organs. Due to its lipophilic quality, CBD accumulates in the adipose tissue particularly in patients with high adiposity and is redistributed into the circulation at a later point [14]. The amount used varies in a wide spectrum: administered doses in studies range from 5 – 1,500 mg/day orally up to 30 mg intravenously [15].

CBD does bind to the CB receptors, normally activated by endogenous CBs including anandamide and 2-arachidonylglycerol. There are two specific CB receptors identified. Unlike THC that binds to CB1 receptors that are mostly located in the brain, CBD binds mostly to CB2 receptors that are found on cells of the immune system, which include T and B lymphocytes, macrophages and monocytes which are not as highly expressed in the central nervous system [16].

The activation of those receptors decreases the release of neurotransmitters glutamate, gamma-aminobutyric acid (GABA), serotonin and norepinephrine and provides synaptic control of upstream neurotransmission [17-19].

CBD acts on several other receptor types. Those include receptors of the serotonin system 5HT 1A/2A/3A, glutamate, TRPV-a (vanilloid) receptors, agonist activity on alpha-1 adrenergic receptors as well as mu-opioid receptors [20].

In addition, CBD acts on the adenosine levels by reducing the adenosine reuptake, which has been associated with neuroprotection and anti-inflammatory processes in the brain [21]. CBD also acts directly on the cerebral vasculature by inhibiting the nitric oxide synthase protein expression as well as inhibition of calcium transport across membranes. Through this mechanism it causes vasodilatation [22].

CBD has shown in vitro studies to be a potent inhibitor with cytochrome P450 enzymes such as CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 [23-36]. These enzymes are also responsible for the metabolization of various other medications. Therefore, CBD will most likely interfere with the serum levels of other medications such as antibiotics, antipsychotics, antidepressants and blood thinners as well as many more. Studies about these interactions are yet lacking. The interactions with CBD and other medications are summarized in Table 1 [23-36].

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