# Cannabis Exposure Interactions with Nicotine Effects: Insights from Randomized Studies

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/cannabis-nicotine-acute-effects-randomized-study/
> **Published:** 2026-10-21T09:00:00-04:00 | **Last Modified / Clinically Audited:** 2026-09-17T15:59:39-04:00
> **Clinical Summary:** A randomized IV nicotine trial finds recent cannabis use heightens aversive nicotine effects at higher doses. Dr. Caplan reviews what this means for co-use.

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Table of Contents

- [Clinical Takeaway](#Clinical_Takeaway)
- [#10 Recent cannabis exposure and acute nicotine effects: insights from randomized, double-blind, placebo-controlled intravenous nicotine studies.](#10_Recent_cannabis_exposure_and_acute_nicotine_effects_insights_from_randomized_double-blind_placebo-controlled_intravenous_nicotine_studies)
- [What This Study Teaches Us](#What_This_Study_Teaches_Us)
- [Why This Matters Clinically](#Why_This_Matters_Clinically)
- [Study Snapshot](#Study_Snapshot)
- [Where This Paper Deserves Skepticism](#Where_This_Paper_Deserves_Skepticism)
- [Dr. Caplan’s Take](#Dr_Caplan8217s_Take)
- [Clinical Bottom Line](#Clinical_Bottom_Line)
- [Related](#Related)

#### Clinical Takeaway

Recent [cannabis use](https://cedclinic.com/cannabis-use-patterns-young-adults-social-health/) does not significantly alter the acute subjective effects of intravenous nicotine in tobacco smokers. This finding suggests that recent [cannabis exposure](https://cedclinic.com/extended-human-brain-development-cannabis/) may not impact nicotine cessation outcomes directly through pharmacodynamic interactions.

### #10 Recent cannabis exposure and acute nicotine effects: insights from randomized, double-blind, placebo-controlled intravenous nicotine studies.

**Citation:** Costa Gabriel P A et al.. *Recent cannabis exposure and acute nicotine effects: insights from randomized, double-blind, placebo-controlled intravenous nicotine studies.*. The international journal of neuropsychopharmacology. 2026. PMID: 42189934.

**Study type:** Journal Article, Randomized Controlled Trial  | 
 **Topic area:** [Drug Interactions](https://cedclinic.com/geriatric-cannabis-use-clinical-considerations-workshop/)  | 
 **CED Score:** 12

Design: 5 Journal: 2 N: 1 Recency: 3 Pop: 2 Human: 1 Risk: -2

**Quality Gate Alerts:**
- Preclinical only

**Abstract:** OBJECTIVE: Cannabis-nicotine co-use is common and may affect cessation outcomes, yet whether recent cannabis exposure alters nicotine’s [acute effects](https://cedclinic.com/episodic-memory-cannabis-impairment-study/) in humans remains unclear. We examined whether recent, non-daily cannabis exposure modulates the acute subjective effects of intravenous (IV) nicotine. METHODS: We pooled data from 2 randomized, double-blind, placebo-controlled studies using IV nicotine to isolate nicotine’s pharmacodynamics in adults who smoke tobacco cigarettes (N = 60). Participants completed 3 sessions (placebo, 0.1 mg, 0.2 mg nicotine/70 kg). Recent cannabis exposure was defined a priori (past-30-day use with positive urine 11-nor-9-carboxy-delta-9-tetrahydrocannabinol vs no past-30-day use with negative screen). Primary outcomes were peak Drug Effects Questionnaire (DEQ) composites-stimulatory, pleasurable, aversive-within 10 minutes post-infusion. Secondary outcomes included nicotine self-administration behavior (proportion of nicotine choices) and cardiovascular responses (heart rate, blood pressure). Linear mixed-effects models included dose, cannabis exposure, sex, and FTND. RESULTS: Nicotine increased all DEQ domains dose-dependently (P 

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Former CMO Canna Care Docs (250,000+ patients supervised), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).