Pharmacokinetic and pharmacodynamic properties of aerosolized (“vaped”) THC in adolescent male and female rats

Ruiz, Christina M.; Torrens, Alexa; Lallai, Valeria; Castillo, Erik; Manca, Letizia; Martinez, Maricela X.; Justeson, D. N.; Fowler, Christie D.; Piomelli, Daniele; Mahler, Stephen V.

doi:10.1007/s00213-021-05976-8

Cited by 40 publications

(34 citation statements)

References 60 publications

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“…In comparison, two human laboratory studies using vaporized cannabis resulted in a C max of 14 ng/ml THC (25 mg dose) 26 and 47 ng/ml THC (50 mg dose) 27 . Our ranges of THC levels in plasma are comparable to what has been shown after IP injection of low doses of THC 0.5-3 mg/kg (∼25-75 ng/ml) 28-30 , after passive THC vapor exposure (35-73 ng/ml) 17, 28, 31 , and in rats self-administering THC vapor puffs (∼10-40 ng/ml) 32, 33 . Blood levels of THC following vapor exposure peak rapidly, within 5-10 minutes after exposure 28, 31 .…”

Section: Discussionsupporting

confidence: 86%

“…Our ranges of THC levels in plasma are comparable to what has been shown after IP injection of low doses of THC 0.5-3 mg/kg (∼25-75 ng/ml) 28-30 , after passive THC vapor exposure (35-73 ng/ml) 17, 28, 31 , and in rats self-administering THC vapor puffs (∼10-40 ng/ml) 32, 33 . Blood levels of THC following vapor exposure peak rapidly, within 5-10 minutes after exposure 28, 31 . Blood levels of the key THC metabolites 11-OH-THC and THC-COOH were relatively low 7-11 and 8-13 ng/ml, respectively, mirroring what has been shown previously with vapor exposure models 28 .…”

Section: Discussionsupporting

confidence: 86%

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Δ⁹-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Moore

Davis

Weerts

2021

Preprint

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Background: Vaping of cannabis and cannabis extracts containing Δ9-tetrahydrocannabinol (THC, the primary psychoactive constituent of cannabis) is on the rise. Development of animal models using vapor exposure is important for increasing our understanding of the rewarding and aversive effects of vaped cannabinoids. Currently there are limited data on the conditioned rewarding effects of THC vapor in rats, and no studies to date examining sex differences. Methods: Male and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning after exposure to vaporized THC or vehicle (propylene glycol, PG). THC vapor-conditioned rats received one of three THC vapor exposure amounts (THC Group 1: 5 puffs of 100 mg/ml THC, THC Group 2: 5 puffs of 200 mg/ml THC, or THC Group 3: 10 puffs of 200 mg/ml THC) and matched vehicle vapor (PG) exposure and on alternate days for two sets of 8 daily sessions (16 days total). Vehicle-conditioned rats (Veh Group 0) received only PG vapor exposure each day. Rats were passively administered vapor for 30-min immediately before daily, 30-min conditioning sessions. Untreated rats completed place preference tests after the 8th and 16th conditioning sessions and then testing continued daily until extinction occurred. Following extinction, rats underwent a THC vapor-primed reinstatement session. Results: Male and female rats showed an exposure-dependent preference for the THC vapor-paired chamber, though sex differences were observed. The lowest THC vapor exposure group tested (THC Group 1) did not produce CPP in males or females. Exposure to the middle condition tested (THC Group 2) resulted in preference for the THC vapor-paired chamber in males, but not females. The highest THC vapor exposure condition tested (THC Group 3) produced place preference in both males and females. Preference for the THC-paired chamber extinguished more quickly in males than in females. Following extinction, THC vapor re-exposure (i.e., drug-prime) did not result in reinstatement of place preference for either sex. Conclusion: This study demonstrated conditioned rewarding effects of THC vapor in both male and female rats, and provides evidence for sex differences in doses of THC vapor that produce CPP and in time to extinction. Conditioned place aversion was not observed at any of the THC vapor exposure amounts tested. These data provide a foundation for future exploration of the conditioned rewarding effects vaporized THC, cannabis and its constituents in preclinical models.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 86%

Δ⁹-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Moore

Davis

Weerts

2021

Preprint

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 86%

“…Our ranges of THC levels in plasma are comparable to what has been shown after IP injection of low doses of THC 0.5-3 mg/kg (~25-75 ng/ml) [28][29][30] , after passive THC vapor exposure ng/ml) 17,28,31 , and in rats self-administering THC vapor puffs (~10-40 ng/ml) 32,33 . Blood levels of THC following vapor exposure peak rapidly, within 5-10 minutes after exposure 28,31 . Blood levels of the key THC metabolites 11-OH-THC and THC-COOH were relatively low 7-11 and 8-13 ng/ml, respectively, mirroring what has been shown previously with vapor exposure models 28 .…”

Section: Discussionsupporting

confidence: 86%

Δ⁹-Tetrahydrocannabinol Vapor Exposure Produces Conditioned Place Preference in Male and Female Rats

Moore

Davis

Sempio

et al. 2024

Cannabis and Cannabinoid Research

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Background: The use of place conditioning procedures and drug vapor exposure models can increase our understanding of the rewarding and aversive effects of vaped cannabis products.Currently there are limited data on the conditioned rewarding effects of vaporized Δ 9tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis in rats, and no studies to date examining sex differences.Methods: Male and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning sessions immediately after exposure to THC or vehicle (propylene glycol, PG) vapor. Locomotor activity was measured by beam breaks during conditioning sessions. THC vapor-conditioned rats received one of three THC vapor exposure amounts (low: 5 puffs of 100 mg/ml THC, medium: 5 puffs of 200 mg/ml THC, or high: 10 puffs of 200 mg/ml THC) and matched vehicle vapor (PG) exposure on alternate days for 16 daily sessions. A 'no THC' control group of vehicle-conditioned rats received only PG vapor exposure each day. After the 8th and 16th conditioning sessions, untreated rats were tested for conditioned place preference (CPP) or avoidance (CPA). Next, extinction tests and a THC vapor-primed reinstatement test were conducted.Results: THC vapor produced CPP and locomotor effects in an exposure dependent manner, and some sex differences were observed. Low THC vapor exposure did not produce CPP in males or females. Medium THC vapor exposure produced CPP in males, but not females. High THC vapor exposure produced CPP in both males and females. Medium and high THC vapor exposure amounts produced hyperactivity in female rats, but not male rats. CPP was more resistant to extinction in females than males. THC vapor re-exposure (i.e., drug-prime) after extinction did not result in reinstatement of CPP for either sex. Conclusion:This study demonstrates conditioned rewarding effects of THC vapor in both male and female rats and provides evidence for sex differences in amounts of THC vapor that produce CPP and in time to extinction. CPA was not observed at any of the THC vapor

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“…However, since only part of the smoked cannabis enters the lungs, the actual inhaled amount is less. 16,17 Therefore, precisely determining the amount absorbed into the bloodstream is difficult.…”

Section: Phase 2: Smoked Cannabis Dosingmentioning

confidence: 99%

Comparing Sublingual and Inhaled Cannabis Therapies for Low Back Pain: An Observational Open-Label Study

Robinson¹,

Ritter²,

Yassin³

2022

Rambam Maimonides Med J

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Background and Objective: Medical cannabis is becoming an acceptable treatment modality in medicine, especially for pain relief. Concurrently, cannabis use is becoming more prevalent worldwide, a public demand-driven trend despite the lack of established scientific basis. This observational open-label study sought to investigate the effectiveness of cannabis therapy for alleviating low back pain symptoms. Methods: Two types of cannabis treatment modalities were sequentially administered to chronic low back pain patients. After an initial 1-month washout period (WO1), the first modality was cannabidiol (CBD)-rich sublingual extract treatment administered for 10 months. Following another washout period, the second modality, Δ⁹-tetrahydrocannabinol (THC)-rich smoked inflorescence (whole dried cannabis flowers) was administered for 12 months. Results: Enrolled in the study were 24 patients whose advanced imaging studies (i.e. computerized tomography or magnetic resonance imaging of the lumbar spine) revealed disc herniation or spinal stenosis. Three patients dropped out of extract therapy treatment but resumed study participation to receive THC-rich smoking therapy. After a minimum of 2 years, cannabis therapy had reduced lower back pain symptoms, as assessed by Oswestry Disability Index, the SF-12 patient-reported outcome questionnaire, and the visual analogue scale. Pain reduction was not significant during the extract treatment part of the study; however, pain reduction was significant during the inhaled therapy part of the study. Conclusions: Our findings indicate that inhaled THC-rich therapy is more effective than CBD-rich sublingual extract therapy for treating low back pain and that cannabis therapy is safe and effective for chronic low back pain.

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Pharmacokinetic and pharmacodynamic properties of aerosolized (“vaped”) THC in adolescent male and female rats

Cited by 40 publications

References 60 publications

Δ⁹-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Δ⁹-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Δ⁹-Tetrahydrocannabinol Vapor Exposure Produces Conditioned Place Preference in Male and Female Rats

Comparing Sublingual and Inhaled Cannabis Therapies for Low Back Pain: An Observational Open-Label Study

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Pharmacokinetic and pharmacodynamic properties of aerosolized (“vaped”) THC in adolescent male and female rats

Cited by 40 publications

References 60 publications

Δ9-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Δ9-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Δ9-Tetrahydrocannabinol Vapor Exposure Produces Conditioned Place Preference in Male and Female Rats

Comparing Sublingual and Inhaled Cannabis Therapies for Low Back Pain: An Observational Open-Label Study

Contact Info

Product

Resources

About

Δ⁹-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Δ⁹-tetrahydrocannabinol (THC) vapor exposure produces conditioned place preference in male and female rats

Δ⁹-Tetrahydrocannabinol Vapor Exposure Produces Conditioned Place Preference in Male and Female Rats