Clinicians’ Guide to Cannabidiol and Hemp Oils

Abstract

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.



Abbreviations and Acronyms:

BCP (β-caryophyllene), CBD (cannabidiol), DEA (Drug Enforcement Administration), ECS (endocannabinoid system), FDA (Food and Drug Administration), THC (tetrahydrocannabinol)


Article Highlights:

  • Cannabidiol (CBD) is a nonintoxicating compound extracted from Cannabis sativa plants that has gained popularity for medical uses ranging from epilepsy to pain control and addiction treatment because of its differing mechanism of action from marijuana and its safety profile.

  • Although important preclinical and pilot human studies have suggested a potential role for CBD in numerous clinical situations, thorough clinical studies have only been performed on intractable epilepsy syndromes for which Epidiolex, a CBD drug, was approved by the US Food and Drug Administration for use.

  • The legal landscape of CBD remains complex because of differing state and federal laws giving access to medical hemp and marijuana products.

  • The CBD and hemp oil product market remains a concerning one because of noted variability in CBD and tetrahydrocannabinol levels in products, as well as lack of regulation in production and distribution.

  • Although CBD and hemp oils remain an unproven therapeutic option, physicians should remain open to the possible future role these products may play in the management of a variety of difficult to treat diseases, in particular pain and addiction treatment in the context of the opioid crisis.


One of the biggest challenges facing health care today is combatting opioid abuse, with medical and nonmedical overuse of opioids exacting a huge toll on society in recent years. Although there has been a larger focus on reducing opioid prescriptions an preventing nonmedical use of opioids, there is an increasing interest in finding more treatment options for patients in pain, and the diverse field of integrative medicine has been finding an increasing role in this area. One promising area has been use of the plant Cannabis sativa, both in medical marijuana as well as hemp and cannabidiol (CBD) oils, with some evidence that access to medical marijuana is correlated with a decrease in opioid use, although there has been controversy about the risks and benefits of encouraging poorly regulated medical use of a known substance of abuse. Cannabidiol and hemp oils have become especially popular because of their low tetrahydrocannabinol (THC) levels, resulting in attributed medical benefits without the “high” of marijuana. However, clinicians have concerns about whether these treatment options are legal, safe, and effective and are largely unfamiliar with these products.Therefore, we provide an overview of the scientific work on cannabinoids, CBD, and hemp oil and clarify the distinction between marijuana, hemp, and the different components of CBD and hemp oil products so that clinicians may be able to direct their patients to the safest and most evidence-based products.

Cannabis sativa has long been utilized by human populations across the world for its therapeutic properties, from pain relief to treatment of epilepsy.Marijuana and hemp are 2 strains of the same plant, C sativa, with marijuana being cultivated over the years for its THC content and hemp for its myriad other uses including paper, clothing, and food.Despite considerable sociopolitical obstacles, scientific understanding of C sativa has progressed substantially in the past 30 years as the many active ingredients of the C sativa strains were isolated and major discoveries were made regarding the body’s own endogenous cannabinoids and the endocannabinoid system (ECS).


The Endocannabinoid System

It is now known that the ECS is globally involved in maintaining homeostasis in the body, connecting all of the body’s organs and systems. The ECS has been implicated in a variety of disease states and important regulatory functions, from chronic inflammatory conditions and regulation of immune homeostasis in the gut to anxiety and migraines. Although the body has its own endogenous cannabinoids, most notably anandamide and 2-arachidonylglycerol, plant-derived cannabinoids (phytocannabinoids) have been researched as potential therapeutic options in a variety of areas because of their modulation of the ECS. Figure below summarizes the basic molecular biology of the ECS, as well as some of the molecular effects of phytocannabinoids.



Phytocannabinoids

Although the body contains its extensive ECS that works through endogenous cannabinoids, many plant-derived cannabinoids have been discovered that act on the ECS as well. The first ones were discovered in the context of C sativa research, with more than 80 phytocannabinoid compounds being discovered in the marijuana plant alone. Phytocannabinoids and other important C sativa components such as terpenoids have now also been documented in a variety of other plants and foodstuffs, such as carrots, cloves, black pepper, ginseng, and Echinacea. The most notable and well-understood phytocannabinoids are THC and CBD, the most common phytocannabinoids in marijuana and hemp strains, respectively. Tetrahydrocannabinol has been noted to work mostly through the CB1 receptor as an agonist, leading to its well-known intoxicating effects. Cannabidiol, on the other hand, has been found to work through a variety of complex pharmacological actions, such as inhibition of endocannabinoid reuptake, transient receptor potential vanilloid 1 and G protein–coupled receptor 55 activation, and increasing the activity of serotonin 5-HT1A receptors. Cannabidiol’s minimal agonism of the CB receptors likely accounts for its negligible psychoactivity when compared with THC.

Figure below summarizes the different endocannabinoids, phytocannabinoids, and synthetic cannabinoids. The synthetic cannabinoids are laboratory-derived THC preparations that have been US Food and Drug Administration (FDA) approved for various usages, as well as nabiximols, which is a nonsynthetic 1:1 THC and CBD preparation that has been approved in the United Kingdom for pain and spasticity related to multiple sclerosis. Nabiximols is not approved by the FDA. Notably, there are many other components in hemp extracts, and many products boast of being “full-spectrum” in retaining these other components, each with their own attributed effects that are theorized to synergize through what is termed the entourage effect—essentially that the whole plant is greater than the sum of its parts.