Entries by Michelle Smith

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Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1–18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

Assessing rates and predictors of cannabis-associated psychotic symptoms across observational, experimental and medical research

Cannabis, one of the most widely used psychoactive substances worldwide, can give rise to acute cannabis-associated psychotic symptoms (CAPS). While distinct study designs have been used to examine CAPS, an overarching synthesis of the existing findings has not yet been carried forward. To that end, we quantitatively pooled the evidence on rates and predictors of CAPS (k = 162 studies, n = 210,283 cannabis-exposed individuals) as studied in (1) observational research, (2) experimental tetrahydrocannabinol (THC) studies, and (3) medicinal cannabis research. We found that rates of CAPS varied substantially across the study designs, given the high rates reported by observational and experimental research (19% and 21%, respectively) but not medicinal cannabis studies (2%). CAPS was predicted by THC administration (for example, single dose, Cohen’s d = 0.7), mental health liabilities (for example, bipolar disorder, d = 0.8), dopamine activity (d = 0.4), younger age (d = −0.2), and female gender (d = −0.09). Neither candidate genes (for example, COMT, AKT1) nor other demographic variables (for example, education) predicted CAPS in meta-analytical models. The results reinforce the need to more closely monitor adverse cannabis-related outcomes in vulnerable individuals as these individuals may benefit most from harm-reduction efforts.

Understanding the epidemiology and perceived efficacy of cannabis use in patients with chronic musculoskeletal pain

The belief that cannabis has analgesic and anti-inflammatory properties continues to attract patients with chronic musculoskeletal (MSK) pain towards its use. However, the role that cannabis will play in the management of chronic MSK pain remains to be determined. This study examined 1) the rate, patterns of use, and self-reported efficacy of cannabis use among patients with chronic MSK pain and 2) the interest and potential barriers to cannabis use among patients with chronic MSK pain not currently using cannabis.


Cannabis and Driving in Older Adults

Question: What is the association between retail cannabis available to the consumer, driving, and associated blood tetrahydrocannabinol (THC) levels in people over 65 years of age? Findings: In this cohort study, 31 regular users of cannabis aged 65 to 79 years chose on average high potency (18.74% THC) THC-dominant cannabis. Weaving was increased and speed was decreased at 30 minutes after smoking, which was not correlated with blood THC concentrations; subjective experience and self-reports of impaired driving persisted for 3 hours. Meaning: These findings suggest that older drivers, even if they regularly use cannabis, show evidence of impaired driving performance after smoking cannabis.


Cannabidiol for behavior symptoms in Alzheimer’s disease (CANBiS-AD): a random- ized, double-blind, placebo-controlled trial

There are currently no safe and effective approved medications for behavioral and psychological symptoms of dementia (BPSD). Cannabidiol (CBD), a non-intoxicating cannabinoid, with anti-anxiety and anti-psychotic properties shows promise To evaluate the feasibility and obtain preliminary evidence in support of a future fully powered efficacy trial of CBD, we carried out a phase 2a, single-site, parallel-group, double-blind, placebo-controlled, randomized trial in patients with Alzheimer’s disease (AD) and BPSD (EudraCT Number – 2019-002106-52). To evaluate the feasibility and obtain preliminary evidence in support of a future fully powered efficacy trial of CBD, we carried out a phase 2a, single-site, parallel-group, double-blind, placebo-controlled, randomized trial in patients with Alzheimer’s disease (AD) and BPSD (EudraCT Number – 2019-002106-52). Participants of either sex aged 55 years or older with possible or probable AD (McKhann et al., Reference McKhann, Drachman, Folstein, Katzman, Price and Stadlan1984) were eligible, if they had BPSD with total score on Neuropsychiatric Inventory (NPI) (Cummings, Reference Cummings1997) ≥4 and at least 1 item with score of 2 or more (frequency × severity) on one of the domains of anxiety, agitation, hallucinations, or delusions.


Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer’s disease symptoms: a case report

This report addresses the beneficial effect of cannabinoids in microdoses on improving memory and brain functions of a patient with mild-stage Alzheimer’s disease. The patient is a 75-year-old white man presenting with main symptoms of memory deficit, spatial and temporal disorientation, and limited daily activity. The experimental therapeutic intervention was carried out for 22 months with microdoses of a cannabis extract containing cannabinoids. Clinical evaluations using Mini-Mental State Examination and Alzheimer’s Disease Assessment Scale-Cognitive Subscale were performed.


Association Between Cannabis Use and Subjective Cognitive Decline: Findings from the Behavioral Risk Factor Surveillance System (BRFSS)

Cannabis consumption has rapidly increased in the United States due to more states legalizing non-medical and medical use. There is limited research, however, investigating whether cannabis may be associated with cognitive function, particularly across multiple dimensions of cannabis use. The objective of this study was to examine whether cannabis consumption reason, frequency, and method are associated with subjective cognitive decline (SCD).

Medical Cannabis Is Not Associated with a Decrease in Activities of Daily Living in Older Adults

The proportion of older adults using medical cannabis is rising. Therefore, we aimed to assess the effects of herbal medical cannabis on the functional status of older adults. We conducted a prospective observational study of patients aged 65 years or older that initiated cannabis treatment for different indications, mostly chronic non-cancer pain, during 2018–2020 in a specialized geriatric clinic. The outcomes assessed were activities of daily living (ADL), instrumental activities of daily living (IADL), pain intensity, geriatric depression scale, chronic medication use, and adverse events at six months. A cohort of 119 patients began cannabis treatment: the mean age was 79.3 ± 8.5 and
74 (62.2%) were female. Of the cohort, 43 (36.1%) experienced adverse effects due to cannabis use and 2 (1.7%) required medical attention. The mean ADL scores before and after treatment were 4.4 ± 1.8 and 4.5 ± 1.8, respectively (p = 0.27), and the mean IADL scores before and after treatment were 4.1 ± 2.6 and 4.7 ± 3, respectively (p = 0.02). We concluded that medical cannabis in older adults has a number of serious adverse events, but was not associated with a decrease in functional status, as illustrated by ADL and IADL scores after six months of continuous treatment.

The Intoxication Equivalency of 11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) Relative to Δ9-tetrahydrocannabinol (THC)

In this study we establish that the primary metabolite of THC – 11-OH-THC – displays equal or greater activity than THC in a mouse model of cannabinoid activity when directly administered and even when accounting for route of administration, sex, pharmacokinetic, and pharmacodynamic differences. These data provide critical insight into the bioactivity of THC metabolites that will inform the interpretation of future cannabinoid research and represent a model for how THC consumption and metabolism may affect cannabis use in humans.


The Use of Cannabinoids in Pediatric Palliative Care—A Retrospective Single-Center Analysis

This data analysis aimed to systematically analyze a pediatric patient population with a life-limiting disease who were administered cannabinoids. It was a retrospective single-center analysis of patients under supervision of the specialized outpatient pediatric palliative care (SOPPC) team at the Department of Pediatrics and Adolescent Medicine of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). Thirty-one patients with a primary diagnosis of neuropediatric, oncologic, metabolic, and cardiologic categories were included. The indications we identified were spasticity, pain, restlessness, anxiety, loss of appetite, epilepsy, and paresis. Certain aspects of quality of life were improved for 20 of 31 patients (64.5%). For nine patients (29%), no improvement was detected. No conclusions could be drawn for two patients (6.5%). Adverse events were reported for six of the thirty-one patients (19.4%). These were graded as mild, including symptoms such as restlessness, nausea, and behavioral issues. We detected no clinically relevant interactions with other medications. We collected fundamental data on the use of cannabinoids by pediatric palliative patients. Cannabinoids are now frequently administered in pediatric palliative care. They seem to be safe to use and should be considered an add-on therapy for other drug regimens.