Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review

Abstract

Cannabidiol, a non-intoxicating phytocannabinoid, has potential therapeutic effects over a broad range of disorders. Recently, there has been increased interest in CBD, as several studies showed promising anticonvulsant efficacy with few side effects. In 2018, a CBD-based oral solution, Epidiolex®, was approved by the FDA to treat two severe forms of pediatric epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Although only these two syndromes are recognized indications for CBD, it has been consumed in an unregulated fashion for a variety of indications including chronic pain, muscle stiffness, inflammation, anxiety, smoking cessation, and even cancer. While CBD legislation in the USA is confusing due to the differences in state and federal laws, CBD has proliferated in the US market in several forms such as CBD oil or capsules, hemp oil/extract, and also as an ingredient in several dietary supplements, syrups, teas, and creams. With the ever-increasing use of CBD and its widespread availability to the general public, it is important to examine and report on possible drug-drug interactions between CBD and other therapeutic agents as well as addictive substances such as alcohol and tobacco. A detailed literature search for CBD's possible interactions was conducted using online databases. As expected, CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol. This review provides a comprehensive list of interacting drugs. The possible mechanisms for these drug-drug interactions are presented in table format. Given the growing popularity of CBD as a medication and the dearth of available information on CBD drug-drug interactions, it is critical to be aware of current drug-drug interactions and it will be important to investigate the impact of CBD upon concomitant medication use in future randomized, controlled trials.

Keywords: cannabidiol; cannabinoids; cytochrome P450; drug–drug interactions; mechanism.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.

Figure 1

a Target-mediated drug–drug interactions of cannabidiol with cannabinoid and 5-hydroxytryptamine 1A receptors. b Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 2A receptors. c Target-mediated drug–drug interactions of cannabidiol with 5-hydroxytryptamine 3A receptors. d Target-mediated drug–drug interactions of cannabidiol with prostaglandin G/H synthase 1 and 2 inhibitors. e Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1B1 and 3A5 inhibitor. f Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 2D6 and 3A7 inhibitor. g Target-mediated drug–drug interactions of cannabidiol with Cytochrome P450 1A2 inhibitor. The red dotted lines indicate CBD’s mechanism/actions as listed in red boxes. The blue double-headed arrows indicate the possible targets and interactions of CBD with other targets/mechanisms as listed in blue boxes. Green single-headed arrows indicate the drugs that act on these targets, as listed in green boxes. Such drugs may have additive/synergistic or antagonistic effects if given concomitantly with CBD.