CBD and Drug Interactions: Trazodone in Focus

Drug-drug interactions and cannabidiol

Following the approval of Epidiolex for the treatment of Epilepsy in 2018, modern medicine has received a much-publicized boost. Within the first launch year, this cannabis-based drug was sold in large units as consumption immediately soared. First-year sales reportedly added $269 million to the global sales of CBD-based pharmaceuticals and supplement products. In the U.S. alone, GW Pharmaceuticals reported a sale value amounting to $106.1 million, as Epidiolex also gathered $10 million in Germany and the UK. Judging from the consumption rate and Epidiolex success in rare forms of epilepsy, it is safe to conclude that cannabis-derived drugs have formed a niche in modern medicine. 

Before the FDA officially approved cannabidiol, many medical experts and integrative healthcare providers have used cannabidiol in adjunct therapy plans for the management of chronic pain, sleep disorders, depression, muscle fatigue, anxiety, and neurobehavioral disorders. Although the 2018 Farm Bill Act officially decriminalized hemp-derived cannabidiol, cannabis and marijuana remain as a Schedule 1 substance. Maintaining the controlled status of cannabis has not affected the global use of cannabidiol and cannabis-derived products. The World Anti-Doping Agency (WADA) has also removed cannabidiol from the list of prohibited substances in sports. In all, many people are officially using cannabidiol and cannabis-derived products compared to the last decade. 

Cannabidiol interactions with other drugs

Cannabidiol exerts its pharmacological properties by modulating the actions of the endocannabinoid system. This system is known to play principal roles in memory formation, mood regulation, metabolic process control, glucose metabolism, and the brain reward system. The cannabinoid receptors are widely distributed in the brain, spinal cord, immune-modulating cells, peripheral tissues, microglia, and vascular elements. Cannabidiol latches on to these receptors an effect a physiological change that generally affects the biological system. The effect observed depends on the location of the receptors. In the brain, cannabidiol decreases the neuronal excitability of the brain cells to treat epilepsy.

As a natural cannabinoid with proven biochemical action in the body, cannabidiol is expected to interact with the action of co-administered drugs. Many research studies have studied the effects of co-administering cannabidiol with other drugs in animal models. Available reports suggested that cannabidiol moderately affects the functionality of the Cytochrome P450 enzymes—a group of membrane-bound enzymes reportedly responsible for the metabolism of about 90% of the total drugs currently in use. These enzymes are important for the elaborate process of drug metabolism. By affecting how the cytochrome P450 enzymes work, cannabidiol can influence the effects of drugs in the body. 

In 2013, Drug Metabolism and Pharmacokinetics published the report of research investigating the inhibitory effects of cannabidiol on the catalytic activity of cytochrome p450 isoforms. Results published indicated that cannabidiol is a potent inhibitor of the cytochrome enzymes and, as such, can affect the bioavailability of drugs metabolized by these enzymes (Rongrong Jigang et al., 2013). This conclusion validates the report of earlier research suggesting that cannabidiol markedly inhibits the metabolism of drugs in animal models by inactivating specific cytochrome p450 enzymes. In addition to its effects on the cytochrome enzymes, there are other research findings suggesting that cannabinoids can influence the activity of other enzyme systems in the body to affect the activity of co-administered drugs.  

Effects of cannabidiol-Trazodone combination

In 2010, the Food Drug Administration approved Oleptro (Trazodone) as an antidepressant for the management of major depressive disorders. Since its approval, Trazodone has also been used as an off-label medication for sleep disorders and PTSD. Trazodone works by inhibiting the biological activity of serotonin transported and serotonin type 2 receptors. In comparison with other popular antidepressants, trazodone has shown better efficacy and few side effects. This drug is particularly popular in the management of depression as it is better tolerated by patients. In addition to its antidepressant properties, Trazodone has also shown significant anti-inflammatory properties. 

Currently, Trazodone is used in combination therapy and can also be used in mono-therapy plans. Lately, there have been many inquiries on the effects of combining cannabidiol oil and Trazodone in the management of depression. In many cases, Trazodone is prescribed for patients who are currently on multiple drugs. Old patients who use cannabidiol oil for pain management might also be placed on Trazodone for the management of depression. Following reports of unexpected adverse effects in patients who are treated with a combination of these drugs, there has been increased interest in the possible interaction between cannabidiol and Trazodone. As a natural cannabinoid with proven antidepressant properties, cannabidiol is logically expected to enhance the actions of antidepressants in a synergistic relationship. 

Judging from recent observations and collated findings in patients, the cannabidiol may increase the adverse effects of Trazodone. Patients who have once combined the two drugs have reported serious cases of dizziness, drowsiness, confusion, and difficulty in concentrating. In aged patients, a combination of Trazodone and cannabidiol may cause impaired cognition and motor coordination difficulties. Although the interaction between Trazodone and cannabidiol has been described as ‘moderate,’ medical experts have advised that the combination should be avoided in patients. Healthcare providers are advised to select alternative medications for depression management in a bid to avoid Trazodone-cannabidiol combination. 

Patients who have recently been treated with cannabidiol oil for pain management are also expected to wait for at least three months before commencing a depression therapy based on Trazodone. In many cases, an alternative antidepressant can be selected for such patients. The science of cannabis keeps expanding rapidly as more researches are conducted to investigate the safety and efficacy of cannabidiol in humans. 

REFERENCES

• https://pubmed.ncbi.nlm.nih.gov/8466552/
• https://www.ncbi.nlm.nih.gov/books/NBK470560/#article-30555.r1
• https://www.drugs.com/drug-interactions/cannabis-with-trazodone-2758-0-2228-0.html
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473892/
• https://www.ncbi.nlm.nih.gov/books/NBK470560/
• https://pubmed.ncbi.nlm.nih.gov/25719754/