California Cannabis Research Briefing, April 2023: Meeting Summary.

On April 28, 2023, the University of California Office of the President, in partnership with the California Department of Cannabis Control (DCC), hosted the California Cannabis Research Briefing. The California Cannabis Research Briefing brought together researchers and state agencies/policymakers to discuss pertinent policy issues on cannabis within the state. Researchers across six different topic areas (environment, cannabis markets, social equity matters, public health, medicinal cannabis use, and public safety) provided brief explanations of their research and its policy implications.

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial.

Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.

Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% Δ9-tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order.

Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial.

Importance: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC.

Objective: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation).

Variable Delta-9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics After Cannabis Smoking in Regular Users.

Background: Despite its federally restricted status, cannabis is widely used medicinally and recreationally. The pharmacokinetics (PK) and central nervous system (CNS) effects of tetrahydrocannabinol (THC), the major psychoactive cannabinoid, are not well understood. The objective of this study was to develop a population PK model of inhaled THC, including sources of variability, and to conduct an exploratory analysis of potential exposure-response relationships.

A longitudinal study of cannabis use and risk for cognitive and functional decline among older adults with HIV.

Cannabis use is rapidly increasing among older adults in the United States, in part to treat symptoms of common health conditions (e.g., chronic pain, sleep problems).

Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.

Background: Cannabis use is a component risk factor for the manifestation of schizophrenia. The biological effects of cannabis include effects on epigenetic systems, immunological parameters, in addition to changes in cannabinoid receptors 1 and 2, that may be associated with this risk. However, there has been limited study of the effects of smoked cannabis on these biological effects in human peripheral blood cells.

The Relationship Between Plasma Tetrahydrocannabinol Levels and Intraocular Pressure in Healthy Adult Subjects.

Background: Δ9-tetrahydrocannabinol (THC) has been shown to decreased intraocular pressure (IOP). This project aims to define the relationship between plasma THC levels and IOP in healthy adult subjects.

Methods: Eleven healthy subjects received a single dose of inhaled cannabis that was self-administered in negative pressure rooms.

Driving Performance and Cannabis Users' Perception of Safety: A Randomized Clinical Trial.

Importance: Expanding cannabis medicalization and legalization increases the urgency to understand the factors associated with acute driving impairment.

Objective: To determine, in a large sample of regular cannabis users, the magnitude and time course of driving impairment produced by smoked cannabis of different Δ9-tetrahydrocannabinol (THC) content, the effects of use history, and concordance between perceived impairment and observed performance.

Design, Setting, And Participants: This double-blind, placebo-controlled parallel randomized clinical trial took place from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California San Diego.

Impact of HIV on Cognitive Performance in Professional Drivers.

Background: The intellectually demanding modern workplace is often dependent on good cognitive health, yet there is little understanding of how neurocognitive dysfunction related to HIV presents in employed individuals working in high-risk vocations such as driving. HIV-associated neurocognitive impairment is also associated with poorer long-term cognitive, health, and employment outcomes.

Setting: This study, set in Cape Town, South Africa, assessed the effects of HIV on neuropsychological test performance in employed male professional drivers.

Tablet-Based Cognitive Impairment Screening for Adults With HIV Seeking Clinical Care: Observational Study.

Background: Neurological complications including cognitive impairment persist among people with HIV on antiretrovirals; however, cognitive screening is not routinely conducted in HIV clinics.

Objective: Our objective for this study was 3-fold: (1) to determine the feasibility of implementing an iPad-based cognitive impairment screener among adults seeking HIV care, (2) to examine the psychometric properties of the tool, and (3) to examine predictors of cognitive impairment using the tool.

Methods: A convenience sample of participants completed Brain Baseline Assessment of Cognition and Everyday Functioning (BRACE), which included (1) Trail Making Test Part A, measuring psychomotor speed; (2) Trail Making Test Part B, measuring set-shifting; (3) Stroop Color, measuring processing speed; and (4) the Visual-Spatial Learning Test.

Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV.

Objective: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.

Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers.

Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆9-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF).

Paresthesia Predicts Increased Risk of Distal Neuropathic Pain in Older People with HIV-Associated Sensory Polyneuropathy.

Objective: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized.

Methods: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations.

The Current State of HIV and Aging: Findings Presented at the 10th International Workshop on HIV and Aging.

With increasing effectiveness of antiretroviral therapy, people with HIV (PWH) are living longer and the prevalence of older PWH continues to increase. Accordingly, PWH are experiencing an increased burden of age-related comorbidities. With this shifting demographics, clinicians and researchers face additional challenges in how to identify, address, and manage the complex intersections of HIV- and aging-related conditions.

Screening for HIV-Associated Neurocognitive Disorders: Sensitivity and Specificity.

HIV-associated neurocognitive disorder (HAND) remains prevalent among people living with HIV (PLWH), especially the mild forms, even those with well-controlled HIV. Recommendations from the literature suggest routine and regular screening for HAND to detect it early and manage it effectively and adjust treatments, if warranted, when present. However, screening for HAND is not routinely done, as there are no current guidelines on when to screen and which test or tests to use.

A Secondary Analysis from a Randomized Trial on the Effect of Plasma Tetrahydrocannabinol Levels on Pain Reduction in Painful Diabetic Peripheral Neuropathy.

This report examines the association between tetrahydrocannabinol (THC) plasma levels and pain response in a secondary analysis of data from a recent diabetic neuropathy study that demonstrated a dose-dependent reduction in spontaneous and elicited pain at specific time points. A randomized, double-blinded, placebo-controlled crossover study was conducted in sixteen patients with painful diabetic peripheral neuropathy. Subjects participated in four sessions, separated by 2 weeks, during each of which they were exposed to one of four conditions: placebo, or 1%, 4%, or 7% THC dose of cannabis.

Assessing HIV provider knowledge, screening practices, and training needs for HIV-associated neurocognitive disorders. A short report.

Management of HIV-associated neurocognitive disorders (HAND) is becoming increasingly important with HIV-positive people living normal life spans. We aimed to establish the level of HAND awareness among doctor and nurse occupational health practitioners, screening used to detect impairment, factors limiting screening for HAND, and training needs. One-hundred-and-five members of the nursing and physician professional societies for occupational health practitioners in South Africa and Occupational Health Departments at five South African universities responded to an email invitation to complete an online survey addressing demographics, HAND knowledge, screeners being used to screen for HAND and related training needs.

Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV.

Background: Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI). Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties.

Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect cannabinoids in whole blood and breath.

Background The widespread availability of cannabis raises concerns regarding its effect on driving performance and operation of complex equipment. Currently, there are no established safe driving limits regarding ∆9-tetrahydrocannabinol (THC) concentrations in blood or breath. Daily cannabis users build up a large body burden of THC with residual excretion for days or weeks after the start of abstinence.

Neurocognitive Impairment in the Combined Antiretroviral Therapy Era in a Romanian Cohort of Young Adults with Chronic HIV Infection.

HIV-associated neurocognitive disorders (HAND) continue to be reported even in patients with successful antiretroviral treatment. We investigated the prevalence of neurocognitive impairment and possible HIV-associated determinants of cognition in a Romanian cohort of young adults, parenterally infected with HIV during their first years of life. Two hundred fourteen treatment-experienced HIV-positive individuals [median age: 24 years, males: 48%, median duration on combined antiretroviral therapy (cART): 12 years] underwent standard immunologic and virological monitoring and antiretroviral resistance testing using pol gene sequencing in both plasma and, when available, cerebrospinal fluid (CSF) paired samples.

A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain.

A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy.

EEG-Based Neurocognitive Metrics May Predict Simulated and On-Road Driving Performance in Older Drivers.

The number of older drivers is steadily increasing, and advancing age is associated with a high rate of automobile crashes and fatalities. This can be attributed to a combination of factors including decline in sensory, motor, and cognitive functions due to natural aging or neurodegenerative diseases such as HIV-Associated Neurocognitive Disorder (HAND). Current clinical assessment methods only modestly predict impaired driving.

Validation of a liquid chromatography-tandem mass spectrometry method for analyzing cannabinoids in oral fluid.

A liquid chromatography tandem mass spectrometry method was developed for quantifying ten cannabinoids in oral fluid (OF). This method utilizes OF collected by the Quantisal™ device and concurrently quantifies cannabinol (CBN), cannabidiol (CBD), Δ-tetrahydrocannabinol (THC), 11-hydroxy-Δ-THC (11-OH-THC), 11-nor-9-carboxy-Δ-THC (THC-COOH), 11-nor-9-carboxy-Δ-THC glucuronide (THC-COOH-gluc), Δ-THC glucuronide (THC-gluc), cannabigerol (CBG), tetrahydrocannabiverin (THCV), and Δ-tetrahydrocannabinolic acid A (THCA-A). Solid phase extraction was optimized using Oasis Prime HLB 30 mg 96-well plates.

Brief Report: Body Mass Index and Cognitive Function Among HIV-1-Infected Individuals in China, India, and Nigeria.

Background: Risk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings.

Methods: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%).