Cannabis and Lorazepam (Ativan)
Generic: lorazepam
Brand names: Ativan
Important Medical Disclaimer
This information is for educational purposes only and does not constitute medical advice. Do not start, stop, or modify your use of Lorazepam or cannabis without consulting your doctor or pharmacist. If you experience adverse effects, seek immediate medical attention. Individual responses to drug combinations vary significantly.
Overview
Lorazepam (Ativan) is an intermediate-acting benzodiazepine used for anxiety, insomnia, seizures, and procedural sedation. Unlike most benzodiazepines, lorazepam undergoes hepatic metabolism primarily through glucuronidation (UGT conjugation) rather than CYP450 oxidation. This gives it a somewhat more favorable pharmacokinetic interaction profile with CBD compared to alprazolam or clonazepam, since CBD's primary drug interaction mechanism is CYP450 inhibition. However, the pharmacodynamic interaction remains significant. The combination of lorazepam and cannabis still produces additive CNS depression, including sedation, motor impairment, and cognitive dysfunction. Both substances enhance GABAergic neurotransmission, and their combined use can lead to excessive sedation. The risk is rated moderate rather than high because the pharmacokinetic interaction is less pronounced, but patients should not mistake this for safety. Additive sedation from this combination can still lead to dangerous impairment, falls, and respiratory compromise, particularly in elderly patients or those taking other CNS depressants. This information is for educational purposes only. Consult your healthcare provider.
How They Interact
Lorazepam is unique among commonly prescribed benzodiazepines in that it is metabolized primarily by UGT2B15-mediated glucuronidation, bypassing the CYP450 system almost entirely. This means that CBD's well-documented inhibition of CYP3A4, CYP2C19, and CYP2D6 has minimal impact on lorazepam clearance. However, emerging research suggests that cannabinoids may also influence UGT enzyme activity, potentially affecting lorazepam metabolism, though this is less well characterized. The primary interaction is pharmacodynamic: lorazepam potentiates GABA-A receptor activity, while THC enhances GABAergic tone through CB1 receptor modulation. CBD may also modulate GABAergic neurotransmission through allosteric effects at GABA-A receptors. The net result is additive sedation and CNS depression, even without a major pharmacokinetic interaction.
Cannabinoid-Specific Interactions
| Cannabinoid | Interaction with Lorazepam |
|---|---|
| CBD | Unlike with other benzodiazepines, CBD has minimal CYP450-mediated interaction with lorazepam because lorazepam is metabolized by glucuronidation. However, CBD has its own sedative properties and may influence UGT enzymes. The additive sedation risk remains clinically relevant. |
| THC | THC and lorazepam both produce sedation, motor impairment, and cognitive dysfunction. Their combination results in additive CNS depression that can significantly impair daily functioning and increase accident risk. THC may also cause paradoxical anxiety, prompting additional lorazepam use. |
| CBN | CBN's sedative properties combined with lorazepam create a risk of excessive drowsiness. Although the CYP450 pharmacokinetic interaction is less relevant for lorazepam, the combined sedative burden of CBN and lorazepam warrants caution. |
Symptoms to Watch For
- ⚠Increased drowsiness or excessive sedation
- ⚠Impaired motor coordination and balance
- ⚠Cognitive slowing and difficulty concentrating
- ⚠Dizziness or lightheadedness upon standing
Recommendations
- 1While the CYP450 interaction is less concerning, additive sedation still makes this combination risky — exercise caution.
- 2Avoid driving or operating machinery when using both substances.
- 3Start with the lowest cannabis dose possible and assess tolerance before increasing.
- 4Inform your prescribing physician about cannabis use so they can evaluate your overall sedative burden.
- 5Be particularly cautious if you are elderly, as the combination significantly increases fall risk.
Research Summary
Lorazepam's glucuronidation-based metabolism is well-established and differentiates it from most benzodiazepines in terms of CYP450-mediated drug interactions. A 2018 study of benzodiazepine drug interactions confirmed that UGT-metabolized benzodiazepines (lorazepam, oxazepam, temazepam) have fewer pharmacokinetic interactions with CYP inhibitors. However, the pharmacodynamic interaction with cannabis remains significant regardless of metabolic pathway. Emergency department data show that benzodiazepine-cannabis combinations, including lorazepam, are associated with increased sedation and psychomotor impairment compared to either substance alone. Emerging research on cannabinoid effects on UGT enzymes may reveal additional interaction mechanisms, but current evidence is preliminary. This information is for educational purposes only. Consult your healthcare provider.
Frequently Asked Questions
Is Ativan safer to combine with cannabis than Xanax?
From a pharmacokinetic perspective, yes — lorazepam bypasses the CYP450 system that CBD inhibits, so there is less risk of elevated drug levels. However, the sedation and CNS depression risks are still significant. 'Safer' does not mean 'safe,' and the combination should still be approached with caution.
Can I take CBD oil with Ativan?
CBD has less pharmacokinetic interaction with lorazepam than with other benzodiazepines because lorazepam is metabolized by glucuronidation rather than CYP450 enzymes. However, CBD has sedative properties that can add to lorazepam's CNS-depressant effects. Discuss this with your doctor.
Does lorazepam interact with marijuana differently than other benzos?
Yes. Lorazepam is metabolized by a different pathway (glucuronidation via UGT enzymes) than most benzodiazepines (CYP3A4). This means CBD's CYP450 enzyme inhibition has less impact on lorazepam levels. However, the additive sedation from combining any benzodiazepine with cannabis remains a concern regardless of metabolism.