Substitution Profile of the Cannabinoid Agonist Nabilone in Human Subjects Discriminating Δ9-Tetrahydrocannabinol

Lile, Joshua A.; Kelly, Thomas C.; Hays, Lon R.

doi:10.1097/wnf.0b013e3181e77428

Cited by 26 publications

(38 citation statements)

References 65 publications

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“…These results are concordant with the ability of CB agonists to impact VDCC function via CB 1 receptor mediated G-protein activation as well as CB-receptor-independent mechanisms (Howlett et al, 2010; Lozovaya et al, 2009). In previous studies, drug discrimination procedures like those used here revealed that the cannabinoid agonist nabilone substituted for Δ 9 -THC, but the dopamine/norepinephrine reuptake inhibitor methylphenidate, the opioid agonist hydromorphone and the GABA A positive allosteric modulators triazolam and diazepam did not, demonstrating the pharmacological selectivity of the Δ 9 -THC discrimination (Lile et al, 2009, 2010, 2014). The present results support this selectivity by demonstrating Δ 9 -THC stimulus generalization to a compound having a common neurobiological target.…”

Section: Discussionsupporting

confidence: 51%

“…To further investigate potential similarities, particularly as they relate to the abuse-related interoceptive effects of cannabis, the present study determined the separate and combined effects of gabapentin and Δ 9 -tetrahydrocananbinol (i.e., Δ 9 -THC, the primary active constituent of cannabis) using pharmacologically selective drug-discrimination procedures (Lile et al, 2009, 2010, 2012, 2014). Gabapentin was hypothesized to occasion Δ 9 -THC-like discriminative-stimulus alone and shift the discriminative-stimulus effects of Δ 9 -THC leftward/upward when administered concurrently.…”

Section: Introductionmentioning

confidence: 99%

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Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol

Lile

Wesley

Kelly

et al. 2016

Behavioural Pharmacology

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The aim of the present study was to examine a potential mechanism of action of gabapentin to manage cannabis-use disorders by determining the interoceptive effects of gabapentin in cannabis users discriminating Δ9-THC using a pharmacologically selective drug-discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received gabapentin (600 and 1200 mg), Δ9-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Δ9-THC served as a discriminative stimulus, produced positive subjective effects, elevated heart rate and impaired psychomotor performance. Both doses of gabapentin substituted for the Δ9-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Δ9-THC when administered alone. When administered concurrently, gabapentin shifted the discriminative-stimulus effects of Δ9-THC leftward/upward, and combinations of Δ9-THC and gabapentin generally produced larger effects on cannabinoid-sensitive outcomes relative to Δ9-THC alone. These results suggest that one mechanism by which gabapentin might facilitate cannabis abstinence is by producing effects that overlap with those of cannabinoids.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol

Lile

Wesley

Kelly

et al. 2016

Behavioural Pharmacology

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“…The observation that women had elevated heart rate and lower skin temperature relative to men is consistent with previously documented differences in women and men for these physiological outcomes (Christensen et al, 2012; Ryan et al, 1994; Umetani et al, 1998). Another possibility is that chronic cannabis administration might result in further sex-based separation in baseline heart rate and skin temperature, considering that these measures are sensitive to acute cannabinoid administration (e.g., Lile et al, 2010b). …”

Section: Discussionmentioning

confidence: 99%

Sex differences in the subjective effects of oral Δ9-THC in cannabis users

Fogel

Kelly²,

Westgate

et al. 2017

Pharmacology Biochemistry and Behavior

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Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ9-tetrahydrocannabinol (Δ9-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ9-THC and placebo and then received a range of Δ9-THC doses (0, 5, 15 and a “high” dose of either 25 or 30 mg). Responses on a drug-discrimination task, subjective effects questionnaire, psychomotor performance tasks, and physiological measures were assessed. Δ9-THC dose-dependently increased drug-appropriate responding, ratings on “positive” visual analog scale (VAS) items (e.g., Good Effects, Like Drug, Take Again), and items related to intoxication (e.g., High, Stoned). Δ9-THC also dose-dependently impaired performance on psychomotor tasks and elevated heart rate. Sex differences on VAS items emerged as a function of dose. Women exhibited significantly greater subjective responses to oral drug administration than men at the 5 mg Δ9-THC dose, whereas men were more sensitive to the subjective effects of the 15 mg dose of Δ9-THC than women. These results demonstrate dose-dependent separation in the subjective response to oral Δ9-THC administration by sex, which might contribute to the differential development of problematic cannabis use.

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“…Fraser7 also noted in this study that nabilone increased sleep time and was not associated with the development of tolerance. Another study by Lile et al8 found similar interoceptive effects of nabilone compared with delta-9-tetrahydrocannabinol, which lead the authors to conclude that nabilone may be useful as a harm reduction approach to reduce use of smoked cannabis in cannabis-dependent individuals similar to the use of agonists in tobacco and opioid dependence. Of note, in an extensive search of scientific literature, popular press, and focused interviews with medical professionals and law enforcement officials, Ware and St Armand9 found little evidence for nabilone abuse, including in Canada where it has been available for over 30 years.…”

mentioning

confidence: 94%

Use of a Synthetic Cannabinoid in a Correctional Population for Posttraumatic Stress Disorder–Related Insomnia and Nightmares, Chronic Pain, Harm Reduction, and Other Indications

Cameron

Watson

Robinson

2014

Journal of Clinical Psychopharmacology

147

101

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Nabilone is a synthetic cannabinoid that has shown promise for the treatment of posttraumatic stress disorder (PTSD)–related insomnia and nightmares as well as efficacy in the management of chronic pain. It has also been proposed for harm reduction in cannabis dependence. Its effectiveness for management of concurrent disorders in seriously mentally ill correctional populations has not been evaluated. This retrospective study of 104 male inmates with serious mental illness prescribed nabilone analyzes the indications, efficacy, and safety of its use. Medications discontinued with the initiation of nabilone were also reviewed. The results showed nabilone targeting a mean of 3.5 indications per patient, thus likely reducing polypharmacy risk. The mean final dosage was 4.0 mg. Results indicated significant improvement in PTSD-associated insomnia, nightmares, PTSD symptoms, and Global Assessment of Functioning and subjective improvement in chronic pain. Medications associated with greater risk for adverse effects or abuse than nabilone were often able to be discontinued with the initiation of nabilone, most often antipsychotics and sedative/hypnotics. There was no evidence of abuse within this high-risk population or reduction of efficacy when nabilone was given in powder form with water rather than as a capsule. This study supports the promise of nabilone as a safe, effective treatment for concurrent disorders in seriously mentally ill correctional populations. Prospective, randomized controlled trials are required to confirm our preliminary results. Follow-up in the community will be required to confirm effectiveness in harm reduction.

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Substitution Profile of the Cannabinoid Agonist Nabilone in Human Subjects Discriminating Δ9-Tetrahydrocannabinol

Cited by 26 publications

References 65 publications

Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol

Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol

Sex differences in the subjective effects of oral Δ9-THC in cannabis users

Use of a Synthetic Cannabinoid in a Correctional Population for Posttraumatic Stress Disorder–Related Insomnia and Nightmares, Chronic Pain, Harm Reduction, and Other Indications

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