Is Gabapentin a Safe and Effective Treatment for Cannabis Use Disorder in Older Adults?

---

Cannabis use vs Gabapentin treatment in elderly: Evidence and clinical considerations

• No FDA-approved pharmacotherapy exists for cannabis use disorder (CUD) in any age group; psychosocial interventions (CBT, motivational interviewing) remain first-line

• Gabapentin has preliminary RCT evidence for reducing cannabis withdrawal, use, and craving in adults, but relevance to elderly patients is uncertain — no trials specifically in older adults, and results from a later fully-powered replication study suggested no advantage over placebo for cannabis abstinence

• Cannabis use in older adults is associated with greater depression, anxiety, cognitive impairment, substance use, cardiovascular events, falls, and short-term mortality

• Daily cannabis users aged ≥50 have 133% increased odds of ≥14 days of poor mental health and 76% increased odds of poor physical health compared to non-users

• Cannabis substantially increases cardiovascular risk: pooled evidence shows increased odds of MI (OR ~1.29), stroke, heart failure, and mortality; risk rises with use frequency

• Gabapentin in elderly carries meaningful risks: dizziness, somnolence, falls, cognitive decline, altered mental status (particularly at higher doses or with CKD), and additive CNS depression with zolpidem

• For the patient specifically: cannabis should be reduced or discontinued; gabapentin at low dose is a reasonable adjunct given his anxiety, insomnia, IBS pain, and cannabis withdrawal support needs — but needs close monitoring for additive CNS effects with zolpidem and cannabis

---

Evidence for cannabis use in older adults

• Perceived benefits (limited and inconsistent)

  • Older adults most commonly use cannabis for chronic pain, insomnia, and anxiety/mood symptoms

  • Some smaller trials suggest modest improvements in pain and sleep in specific populations, but benefit-to-risk ratio is unclear

  • No medical consensus supports cannabis for chronic pain, insomnia, or anxiety in older adults

• Documented harms (consistent evidence)

  • Psychiatric: associated with depression, anxiety, cognitive impairment, amotivation, and increased suicidal ideation in older adults

  • Cognitive: worsened executive function, memory, and attention — compounding age-related decline

  • Cardiovascular: increased risk of MI, stroke, arrhythmias, and heart failure; cannabis smoking within 60 minutes raises MI risk up to 4.8-fold

  • Daily cannabis users ≥50 have 133% higher odds of ≥14 poor mental health days and 76% higher odds of ≥14 poor physical health days

  • Falls, injuries, accidents — heightened in elderly

  • Short-term mortality risk increased in adults ≥65 with positive cannabis screening

  • Polypharmacy interactions — altered pharmacokinetics with aging increases interaction risk

  • Addiction potential: 20–33% of adults who use cannabis develop CUD; risk higher with regular daily use.

Evidence for gabapentin in cannabis use disorder

• Positive preliminary evidence

  • Mason et al. 2012 proof-of-concept RCT (n=50, gabapentin 1200 mg/day for 12 weeks): significant reductions in cannabis use, withdrawal symptoms, craving, improved sleep (PSQI), mood (BDI-II), and executive function vs placebo

  • Mechanism: indirectly modulates GABA and normalizes corticotropin-releasing factor signaling disrupted in cannabis withdrawal

  • Well tolerated in the Mason trial, no evidence of drug substitution

• Limiting evidence

  • Sample sizes are small; high attrition (36% completion in Mason trial)

  • No data specifically in elderly patients

  • Unpublished fully-powered replication study suggested gabapentin was no more advantageous than placebo for achieving cannabis abstinence

  • Cochrane review concludes the evidence base remains weak

  • Risks in elderly (falls, altered mental status, cognitive decline) must be weighed

Evidence for gabapentin in co-morbid conditions

• Anxiety

  • Moderate evidence for gabapentinoids in anxiety states, particularly pre-operative anxiety (SMD -0.92, 95% CI -1.32 to -0.52) and some panic/social phobia

  • Case report evidence for GAD, with dose-response pattern

• Insomnia

  • Evidence is inconclusive for primary insomnia

  • Some studies show improved sleep latency, total sleep time, sleep efficiency in secondary insomnia

• IBS

  • Used off-label, small evidence base

• Pain (IBS-related visceral pain)

  • Well-established efficacy in neuropathic pain; may offer some benefit for visceral pain

---

Pros and cons
Continuing cannabis

• Pros

  May be providing some subjective relief for anxiety and sleep in his perception

• Cons (overwhelming)

  • Compounds his Generalized Anxiety Disorder — contradicts treatment goals

  • Worsens insomnia and disrupts sleep architecture (undermines medications goals)

  • Increases suicide risk — stacks on his other risk factors

  • Cardiovascular risk

  • Cognitive decline — compounds aging-related changes and undermines advance care planning discussions

  • Falls especially with other sedating medications

  • Reinforces existing substance use disorder — worsening his adjustment disorder and addiction trajectory

  • GI distress may worsen with cannabis use

  • Federal/state regulatory risk — Schedule I status

Pros and cons
Gabapentin treatment

• Pros

  • Addresses multiple symptoms simultaneously: cannabis craving/withdrawal, anxiety, sleep, IBS-related discomfort

  • Rationale for low dose: smaller doses still provide benefit with lower risk of altered mental status

  • May facilitate zolpidem or benzodiazepine reduction — a long-term goal for insomnia

  • Well tolerated in Mason trial with minimal side effects

  • May help IBS-related visceral pain — off-label use

• Cons

  • Additive CNS depression (example with zolpidem and cannabis)

  • Fall risk — compounded by his existing zolpidem or benzodiazepine use

  • Renal function not documented — gabapentin is renally cleared; dose adjustment may be needed

  • Misuse risk — elevated with substance use disorder history; monitor for self-dose escalation and early refill requests

  • Altered mental status — dose-dependent in elderly; risk higher with CKD

  • Evidence for abstinence in CUD is limited — may help symptoms but not reliably produce abstinence

  • Florida classifies gabapentin as a controlled substance — requires PDMP monitoring

Clinical recommendation

Reduce cannabis first, then consider gabapentin dose adjustment:

1. Primary goal: discontinue or significantly reduce cannabis use — it is contributing to anxiety, insomnia, cognitive concerns, cardiovascular risk, and undermining treatment.

2. Gabapentin at current low dose (100 mg QID) is reasonable as an adjunct to cannabis reduction, targeting withdrawal symptoms, anxiety, sleep, and IBS pain

3. Strict safety monitoring is needed:
   

   • Falls, gait, sedation (particularly given concurrent zolpidem or sedating medications)

   • Cognitive status at every visit

   • Renal function assessment (baseline BMP with eGFR/CrCl)

   • PDMP review

   • Watch for gabapentin misuse signals in the setting of cannabis use disorder
     

4. Parallel psychosocial interventions: CBT and motivational interviewing, which are first-line for CUD

5. Advance care planning as a modifiable harm-reduction strategy given existential concerns

6. Monitor cardiovascular symptoms closely — any chest pain, palpitations, syncope requires evaluation given cannabis exposure
   

• Cannabis use in older adults is associated with increased depression, anxiety, cognitive impairment, cardiovascular events, falls, and mortality — outweighs perceived benefits

• Gabapentin + zolpidem + cannabis = additive CNS depression in elderly; monitor for sedation, falls, and respiratory depression

• Gabapentin misuse risk is elevated in patients with cannabis use disorder — watch for dose escalation and early refills