What is the interaction between Gabapentin and Tetrahydrocannabinol (THC)?

From the Guidelines

I strongly advise against combining gabapentin and THC (tetrahydrocannabinol) without medical supervision due to potential interaction risks that could significantly impact morbidity, mortality, and quality of life. Both substances affect the central nervous system and when taken together can cause enhanced sedation, dizziness, confusion, and impaired coordination, which could lead to increased risk of accidents, injuries, or other adverse events. Gabapentin is a prescription medication used to treat seizures, nerve pain, and other conditions, while THC is the psychoactive component in cannabis. The combination may increase side effects like drowsiness, cognitive impairment, and reduced motor control, which could be dangerous when driving or operating machinery 1.

Key Considerations

• The interaction between gabapentin and THC occurs because both substances affect similar neurotransmitter systems in the brain, particularly GABA pathways, which regulate nervous system activity.
• The use of gabapentin and other non-opioid analgesics for chronic pain management is recommended, with careful consideration of their potential side effects and interactions with other substances, including THC 1.
• Medical supervision is crucial when combining gabapentin with THC to evaluate the specific health situation, medication regimen, and provide guidance on timing or dosage adjustments if necessary.
• The potential risks and benefits of combining gabapentin and THC should be carefully weighed, taking into account the individual's medical needs and the potential impact on their quality of life.

Recommendations

• If you're prescribed gabapentin and considering using THC for medical or recreational purposes, consult your healthcare provider first to discuss the potential risks and benefits.
• Your doctor may recommend spacing out doses, adjusting amounts, or avoiding the combination altogether depending on your medical needs and the potential impact on your quality of life.
• Alternative treatments for chronic pain, such as non-opioid analgesics, physical therapy, exercise, stress management, and cognitive behavioral therapy, should be considered and discussed with your healthcare provider 1.

From the Research

Interaction between Gabapentin and Tetrahydrocannabinol (THC)

• The interaction between gabapentin and THC has been studied in various research papers, with a focus on their combined effects on neuropathic pain and potential drug-drug interactions 2, 3, 4, 5, 6.
• A study published in Neuropharmacology in 2019 found that co-administration of THC and gabapentin in a fixed-ratio dose-dependently reduced mechanical and cold allodynia, and produced all the side-effects observed for THC, including motor incoordination, catalepsy, and sedation 2.
• Another study published in the Journal of clinical medicine in 2020 highlighted the potential adverse drug events with THC due to drug-drug interactions, including metabolic interactions with CYP3A4 and CYP2C9, which can be impacted by several common medications 3.
• A study published in Behavioural pharmacology in 2016 examined the separate and combined effects of gabapentin and THC in humans discriminating THC, and found that gabapentin substituted for the THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of THC 4.
• Research published in Neuropharmacology in 2021 found that gabapentin attenuates somatic signs of precipitated THC withdrawal in mice, suggesting that gabapentin may be effective at treating cannabinoid withdrawal symptoms including somatic and affective symptoms 5.
• A nationwide register-based pharmacoepidemiologic comparison published in the European journal of pain in 2022 found that among patients with neuropathic pain, users of THC used more opioids during follow-up than controls, but users of either CBD, THC, or combined CBD + THC used less gabapentin than controls 6.

Effects on Neuropathic Pain

• The combination of THC and gabapentin has been shown to have a synergistic effect on reducing mechanical and cold allodynia in a mouse neuropathic pain model 2.
• Gabapentin has been found to substitute for the THC discriminative stimulus and produce subjective and performance-impairing effects that overlap with those of THC in humans 4.
• Patients with neuropathic pain may benefit from treatment with cannabis-based medicines or medical cannabis, particularly in terms of reduced use of gabapentin and fewer days admitted to hospitals, compared with propensity score matched controls 6.

Drug-Drug Interactions

• THC has been found to have potential adverse drug events due to drug-drug interactions, including metabolic interactions with CYP3A4 and CYP2C9, which can be impacted by several common medications 3.
• Gabapentin has been found to interact with THC, producing a synergistic effect on reducing mechanical and cold allodynia in a mouse neuropathic pain model, and attenuating somatic signs of precipitated THC withdrawal in mice 2, 5.