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The American Journal of Geriatric... Nov 2019To investigate the efficacy and safety of nabilone for agitation in patients with moderate-to-severe Alzheimer's disease (AD). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the efficacy and safety of nabilone for agitation in patients with moderate-to-severe Alzheimer's disease (AD).
DESIGN
This 14-week randomized double-blind crossover trial compared nabilone to placebo (6 weeks each) with a 1-week washout between phases.
SETTING
Patients were recruited from a long-term care facility and geriatric psychiatry clinics.
PARTICIPANTS
Patients had AD (standardized Mini-Mental State Examination [sMMSE ≤24]) and agitation (Neuropsychiatric Inventory-Nursing Home version [NPI-NH]-agitation/aggression subscore ≥3).
INTERVENTION
Nabilone (target 1-2 mg) versus placebo.
MEASUREMENTS
The primary outcome was agitation (Cohen Mansfield Agitation Inventory [CMAI]). Secondary outcomes included NPI-NH total, NPI-NH caregiver distress, cognition (sMMSE and Severe Impairment Battery [SIB] or Alzheimer's Disease Assessment Scale of Cognition), global impression (Clinician's Global Impression of Change [CGIC]), and adverse events.
RESULTS
Thirty-nine patients (mean ± SD age = 87 ± 10, sMMSE = 6.5 ± 6.8, CMAI = 67.9 ± 17.6, NPI-NH total = 34.3 ± 15.8, 77% male, nabilone dose = 1.6 ± 0.5 mg) were randomized. There were no crossover or treatment-order effects. Using a linear mixed model, treatment differences (95% CI) in CMAI (b = -4.0 [-6.5 to -1.5], t(30.2) = -3.3, p = 0.003), NPI-NH total (b = -4.6 [-7.5 to -1.6], t(32.9) = -3.1, p = 0.004), NPI-NH caregiver distress (b = -1.7 [-3.4 to -0.07, t(33.7) = -2.1, p = 0.041), and sMMSE (b = 1.1 [0.1-2.0], t(22.6) = 2.4, p = 0.026) all favored nabilone. However, in those who completed the SIB (n = 25) treatment differences favored placebo (b = -4.6 [-7.3 to -1.8], t(20.7) = -4.8, p = 0.003). CGIC improvement during nabilone (47%) and placebo (23%) was not significantly different (McNemar's test, exact p = 0.09). There was more sedation during nabilone (45%) compared to placebo (16%) phases (McNemar's test, exact p = 0.02), but treatment-limiting sedation was not significantly different (McNemar's test, exact p = 0.22).
CONCLUSIONS
Nabilone may be an effective treatment for agitation. However, sedation and cognition should be closely monitored.
Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Cognition; Double-Blind Method; Dronabinol; Female; Homes for the Aged; Humans; Male; Nursing Homes; Psychiatric Status Rating Scales; Treatment Outcome
PubMed: 31182351
DOI: 10.1016/j.jagp.2019.05.002 -
Pharmacology, Biochemistry, and Behavior Sep 2023Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications.... (Review)
Review
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.
Topics: Humans; Cannabidiol; Cannabinoids; Cannabis; Hallucinogens; Attention Deficit Disorder with Hyperactivity; Dronabinol; Randomized Controlled Trials as Topic
PubMed: 37543051
DOI: 10.1016/j.pbb.2023.173607 -
Medicina (Kaunas, Lithuania) Jun 2020Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms...
BACKGROUND AND OBJECTIVE
Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration.
METHODS
A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans.
RESULTS
The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration.
CONCLUSIONS
Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use.
Topics: Administration, Oral; Dronabinol; Drug Compounding; Humans; Nitrogen Mustard Compounds
PubMed: 32585912
DOI: 10.3390/medicina56060309 -
Current Neuropharmacology 2023During the last two years, hexahydrocannabinol (HHC), the hydrogenated derivative of tetrahydrocannabinol has been freely sold by internet websites as a "legal"...
BACKGROUND
During the last two years, hexahydrocannabinol (HHC), the hydrogenated derivative of tetrahydrocannabinol has been freely sold by internet websites as a "legal" replacement to THC and cannabis in a range of highly attractive branded and unbranded products, some of which are sold as "legal highs". Potentially, there could be a large demand for HHC products by individuals in Europe and internationally.
METHODS
Studies reporting HHC pharmacology, toxicology and analysis were identified from Pubmed and Scopus databases, and official international organizations' websites were considered.
RESULTS
HHC showed the effects of the typical cannabinoid on the central nervous system, with lower potency than Δ-THC. A few studies highlighted that 9(R)-HHC is more potent than 9(S)-HHC. This molecule showed an affinity for cannabinoid receptor CB1 both and , suggesting a possible therapeutic effect in several pathologies. However, the affinity for the CB1 receptor suggests a possible addiction potential, inducing the users to misuse it. Since actual intoxication cases have not yet been reported, the HHC harmful potential was not described, probably due to the lack of effective analytical methods to detect HHC in biological matrices. Conversely, different analytical assays were developed and validated to separate HHC epimers in natural and non-natural sources.
CONCLUSION
Similarly to other NPS, the HHC represents a cheaper alternative to the controlled Δ-THC. Its monitoring is a crucial challenge for toxicological and forensic purposes. To this concern, it is essential to further investigate HHC to support health providers in the identification of related intoxications.
Topics: Humans; Dronabinol; Cannabinoids; Cannabinoid Receptor Agonists; Cannabis; Central Nervous System Agents
PubMed: 37357519
DOI: 10.2174/1570159X21666230623104624 -
Current Opinion in Psychology Apr 2021The aim of this review is to discuss recent evidence on cannabis and driving ability. In particular, the review examines experimental research on the acute effects of... (Review)
Review
The aim of this review is to discuss recent evidence on cannabis and driving ability. In particular, the review examines experimental research on the acute effects of tetrahydrocannabinol (THC) on driving-related neurobehavioral skills and driving performance based on simulator and road course studies. The evidence indicates that certain driving abilities are significantly, albeit modestly, impaired in individuals experiencing the acute effects of THC. Treatment effects are moderated by dose, delivery method, recency of use, and tolerance development, with inconclusive evidence concerning the moderating influence of cannabidiol. Emerging research priorities include linking neurobehavioral deficits to specific decrements in driving performance, estimating the real-world implications of experimental impaired driving research, understanding how tolerance differentially affects driving impairment across subgroups, and developing more evidence on cannabidiol's potential role in mitigating THC-induced impairment.
Topics: Cannabidiol; Cannabis; Dronabinol; Humans
PubMed: 33839427
DOI: 10.1016/j.copsyc.2021.03.003 -
Journal of Adolescent and Young Adult... Apr 2021The therapeutic utility of in cancer is a topic of intense interest. Dronabinol is synthetic Δ-tetrahydrocannabinol (THC), the primary psychoactive component of , and...
The therapeutic utility of in cancer is a topic of intense interest. Dronabinol is synthetic Δ-tetrahydrocannabinol (THC), the primary psychoactive component of , and is approved for treating refractory chemotherapy-induced nausea and vomiting. Little is known about dronabinol prescribing in children and young adults, and no published concentration data are available. This study evaluated national level dronabinol use and assessed concentrations of THC and its primary metabolites in patients with cancer <27 years of age prescribed dronabinol. Observational review of records from the Pediatric Health Information System (PHIS) and a regional network of hospitals in the Intermountain West, including a tertiary care children's hospital, Primary Children's Hospital (PCH), for inpatients <27 years of age prescribed dronabinol. Prospective blood samples were collected from children with cancer at PCH. Across PHIS institutions, overall dronabinol prescribing aligned with the pharmacy records for those with cancer ( < 0.0001), and of these, 10.4% received dronabinol as inpatients. Blood collected within 72 hours of dronabinol administration was available from 10 children with a median age of 12.5 (range 6-17) years. Quantifiable concentrations were found in 4 (13%), 6 (20%), and 1 (3%) samples assayed for THC, 11-nor-9-carboxy-Δ-tetrahydrocannabinol (COOH-THC), and 11-hydroxy-Δ-tetrahydrocannabinol (OH-THC), respectively. THC concentrations ranged between 0.100 and 0.128 ng/mL and were not associated with dose. Dronabinol prescribing appears exclusive to patients diagnosed with cancer, and its use has increased steadily in the past decade. In a small sample of children administered dronabinol, THC and metabolite concentrations were consistently low or undetectable.
Topics: Adolescent; Cannabis; Child; Dronabinol; Gas Chromatography-Mass Spectrometry; Humans; Neoplasms; Prospective Studies; Young Adult
PubMed: 32678694
DOI: 10.1089/jayao.2020.0021 -
CMAJ : Canadian Medical Association... Jun 2019
Review
Topics: Dronabinol; Female; Humans; Infertility; Male; Marijuana Smoking; Ovulation; Sperm Count
PubMed: 31182459
DOI: 10.1503/cmaj.181577 -
Ugeskrift For Laeger Apr 2024In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory... (Review)
Review
In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.
Topics: Humans; Chronic Pain; Medical Marijuana; Dronabinol; Analgesics
PubMed: 38708699
DOI: 10.61409/V08230546 -
Journal of Cystic Fibrosis : Official... Mar 2021
Topics: Aminophenols; Aminopyridines; Benzodioxoles; Cannabinoid Receptor Agonists; Chloride Channel Agonists; Clinical Trials as Topic; Cystic Fibrosis; Dronabinol; Drug Combinations; Humans; Indoles; Quinolones
PubMed: 33408059
DOI: 10.1016/j.jcf.2020.12.017 -
International Journal of Environmental... Apr 2023Cannabis is the most widely used illicit drug in Western counties and its abuse is particularly high in male adolescents and young adults. Its main psychotropic... (Review)
Review
Cannabis is the most widely used illicit drug in Western counties and its abuse is particularly high in male adolescents and young adults. Its main psychotropic component, the cannabinoid delta-9-tetrahydrocannabinol (Δ-THC), interferes in the endogenous endocannabinoid system. This signaling system is involved in the control of many biological activities, including the formation of high-quality male gametes. Direct adverse effects of Δ-THC in male reproduction are well known in both animal models and humans. Nevertheless, the possibility of long-term effects due to epigenetic mechanisms has recently been reported. In this review, we summarize the main advances in the field suggesting the need to pay attention to the possible long-term epigenetic risks for the reproductive health of cannabis users and the health of their offspring.
Topics: Animals; Adolescent; Young Adult; Male; Humans; Cannabis; Dronabinol; Cannabinoids; Hallucinogens; Epigenesis, Genetic
PubMed: 37174181
DOI: 10.3390/ijerph20095663