Cannabis Involvement and Demand in Frequent Concentrate Users Versus Predominantly Flower Users.

OBJECTIVE: Cannabis concentrate products contain more of the intoxicating cannabinoid, tetrahydrocannabinol, than flower products and, thus, may produce greater harm. Indeed, concentrate use is associated with greater cannabis dependence and problems (e.g., anxiety) than flower use. Given this, continued examination of concentrate versus flower use differences on associations with various cannabis measures may be useful. These measures include behavioral economic demand for cannabis (i.e., its subjective reinforcing value), use frequency, and dependence. METHOD: In the present study of 480 cannabis users, those who were frequent concentrate users (n = 176) were compared with predominantly flower users (n = 304) regarding the relationship of two latent drug demand metrics assessed by the Marijuana Purchase Task to cannabis use frequency (i.e., days of cannabis use) and cannabis dependence (i.e., Marijuana Dependence Scale scores). RESULTS: Two previously observed latent factors emerged, based on confirmatory factor analysis: amplitude, reflecting maximum consumption, and persistence, reflecting cost insensitivity. Group comparisons showed that amplitude was greater among the concentrate versus flower group, but no difference was found for persistence. Further, using structural path invariance testing, the factors were differentially associated with cannabis use frequency across groups. Amplitude was positively associated with frequency for both groups, whereas persistence was negatively associated with frequency for the flower group. Neither factor was associated with dependence for either group. CONCLUSIONS: Findings continue to indicate that the demand metrics, although distinct, can be parsimoniously condensed into two factors. In addition, method of administration (i.e., concentrate vs. flower use) may affect how demand for cannabis relates to frequency of use. Associations were notably stronger with frequency relative to dependence.

Effects of a cue associated with cocaine or food reinforcers on extinction and postextinction return of behavior.

Studies of instrumental responding often include the delivery of a cue that is coincident with the delivery of the reinforcer. One purpose of this is for the cue to be removed during extinction and then presented later to assess whether responding returns (cue-induced reinstatement). In two experiments, we examined the effects of having a cue associated with reinforcement present or absent during extinction. In Experiment 1, the cue was associated with fixed ratio responding for intravenous cocaine or food pellets in one context (Context A), followed by extinction in another context (Context B), where responding produced the cue in one group but did not produce the cue in the other group. Afterward, contextual renewal was assessed with and without the cue in Context A. During extinction, a cue previously associated with cocaine reinforcement caused an increase in responding initially (an extinction burst) and throughout 16 2-hr extinction sessions, as well as weakened contextual renewal when animals were tested with the cue in Context A. In contrast, there were few detectable effects of the cue on extinction and contextual renewal when food pellets were the reinforcer. In Experiment 2, effects of a cue during extinction of progressive ratio responding were revealed with food pellets when animals showed weakened responding on the initial trials of postextinction reacquisition sessions. These experiments demonstrate that the presence of a cue associated with reinforcement during extinction may prolong responding in the short term while creating a more persistent form of extinction that resists relapse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Associations between self-reported cannabis use frequency, potency, and cannabis/health metrics.

BACKGROUND: Research shows that cannabis use frequency is associated with cannabis dependence and health metrics. However, much less is known about how self-reported cannabis potency (THC and CBD) may be associated with the same metrics, and whether any associations exist after accounting for frequency of cannabis use. Moreover, even less is known about how these relations may differ across cannabis product forms. This exploratory study examined 1) associations between cannabis frequency, potency, and cannabis/health metrics, and 2) whether associations between potency and cannabis/health metrics remained after controlling for frequency of use. METHODS: Using a sample of adult recreational cannabis users in Colorado (N = 300), we tested the relationship between self-reported cannabis use metrics of frequency and potency of flower, edible, and concentrate products with separate measures of problematic cannabis use (i.e., dependence, withdrawal, craving), depression, anxiety, and general perceived health. RESULTS: Greater frequency of flower and concentrate (but not edible) use were associated with greater problematic cannabis use, and greater concentrate use frequency was also associated with more mental health problems. Partial correlations controlling for average frequency of use across all product forms and CBD potency per product showed that one significant association between THC potency and cannabis/health metrics remained (i.e., higher THC concentrate potency with better health), and one emerged (i.e., higher THC concentrate potency with lower cannabis withdrawal). CONCLUSIONS: Frequency of use is reliably associated with problematic cannabis use for flower and concentrates, but it did not account for all observed associations in this study. Differences in patterns of associations between frequency and potency and cannabis/health metrics across cannabis forms suggest a need for better understanding user reports of THC and CBD potency, individual differences among users, and improved measurement.

Cannabis use and sleep: Expectations, outcomes, and the role of age.

STUDY OBJECTIVES: Determine relationship between cannabis use with 1) expectations of cannabis being a sleep aid, 2) subjective sleep outcomes, and 3) the influence of age on these relationships. METHODS: In 152 moderate cannabis users with a wide age range (67% female, mean age = 31.45, SD = 12.96, age range = 21-70; mean days of cannabis use in prior two weeks = 5.54, SD = 5.25) we examined the influence of cannabis use history and behaviors on expectations of cannabis being a sleep aid and sleep outcomes via the Pittsburgh Sleep Quality Index (PSQI). Moderation analysis examined the role of age in the relationship between cannabis use and sleep outcomes. RESULTS: Endorsing current cannabis use and more days of cannabis use were associated with increased expectations that cannabis use improves sleep (all ß > 0.03, p < 0.04). Frequency of recent use and reported average THC or CBD concentration were largely not associated with sleep outcomes. However, endorsing current cannabis use was associated with worse subjective sleep quality (ß = 1.34, p = 0.02) and increased frequency of consuming edibles was associated with worse subjective sleep efficiency (ß = 0.03, p = 0.04), lower sleep duration (ß = 0.03, p = 0.01), and higher global PSQI scores (worse overall sleep) (ß = 0.10, p = 0.01). Additionally, age had a moderating influence on the relationship between increased self-reported concentration of CBD and both better sleep duration and sleep quality (both p < 0.03). While the main effects of cannabis use on sleep outcomes did not survive multiple comparisons correction test (all p adj > 0.34), the adjusted p values for the main effects of cannabis behaviors/history on expectations of cannabis as a sleep aid (p adj = 0.07-0.09) and the main effects of CBD concentration on sleep duration (p adj = 0.08), as well as the interaction terms of CBD and age for that model (p adj = 0.07), were trending. CONCLUSION: Cannabis users have increased expectations of cannabis being a sleep aid, but few associations existed between cannabis use and sleep outcomes. The two exceptions were endorsing any cannabis use and frequency of edible use. Additionally, age may be an important moderator of the potential positive influence CBD concentration can have on sleep.

Experience of migraine, its severity, and perceived efficacy of treatments among cannabis users.

OBJECTIVES: As the legal and cultural landscape surrounding cannabis use in the United States continues to evolve, more Americans are turning to cannabis to self-medicate a number of ailments, including migraines. The purpose of the present study was to examine patterns of cannabis use and its associated relief among migraineurs. DESIGN: Participants were N = 589 adult cannabis users living in states with full legal access. Using a cross-sectional design, participants completed an online survey assessing their cannabis use profiles, migraine experience, and self-reported relief from cannabis and non-cannabis treatments. RESULTS: 161 participants (27.3 %) reported experiencing migraines. 76.4 % of migraineurs (N = 123) endorsed using cannabis to treat their migraines. 69.9 % (N = 86) of migraineurs using cannabis for migraine relief also endorsed using non-cannabis products (e.g., over-the-counter pain medication, triptans) to treat their migraines. Although their subjective health was similar (p = .17), migraineurs who endorsed using cannabis to treat their migraines reported more severe migraines compared to those who did not (p = .02). Migraineurs reported significantly more migraine relief from cannabis compared to non-cannabis products, even after controlling for migraine severity (p = .03). The majority of migraineurs using cannabis to treat their migraines were not medical cardholders (65.0 %), suggesting that these individuals were self-medicating in lieu of physician guidance. CONCLUSIONS: The present study provides insight into the prevalence of cannabis use for migraine relief in a sample of cannabis users, and suggests that these migraineurs experience a high level of migraine relief from cannabis. Future studies are needed to determine the cannabis forms, potencies, and dosages that are most effective at treating migraine pain.

Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment.

Importance: The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research. Objective: To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis. Design, Setting, and Participants: In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes. Exposures: Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary. Main Outcomes and Measures: Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance. Results: A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) µg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) µg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed. Conclusions and Relevance: This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.

Validation of a multisubstance online Timeline Followback assessment.

OBJECTIVES: The Timeline Followback (TLFB) was originally developed to assess alcohol consumption patterns (American Journal of Public Health, 86, 1996, 966) and has been increasingly modified for Web-based use. Additionally, new modes of substance use administration have emerged, creating a need for an adaptable TLFB tool than can capture data such as cannabis product potency or prescription drug use. Our goal was to validate an online TLFB that reliably assesses a wide range of substances in greater detail. METHODS: Using a within-subjects counterbalanced design, daily substance use data were collected from 50 college students over a 14-day retrospective period using both the traditional in-person TLFB and online TLFB (O-TLFB). RESULTS: All substance use variables, including detailed measures of cannabis metrics, correlated significantly (r's ranged from .653 to .944, p < .001) between TLFB versions. Further, results demonstrated that both the online TLFB and in-person TLFB demonstrated concurrent validity with both the Alcohol Use Disorders Identification Test (AUDIT) and Marijuana Dependence Scale (MDS). CONCLUSION: Overall, the data suggest that this new O-TLFB demonstrates strong reliability and delivers a versatile and secure tool for substance use assessment that is relevant to a variety of biomedical and psychological research contexts.

Acute Effects of Cannabis Concentrate on Motor Control and Speed: Smartphone-Based Mobile Assessment.

Background: The use of cannabis concentrate is dramatically rising and sparking major safety concerns. Cannabis concentrate contains tetrahydrocannabinol (THC) potencies up to 90%, yet there has been little research on motor impairment after concentrate use (commonly referred to as "dabbing"). This study measured postural control and motor speed after the use of high potency concentrates in males and females. Methods: Experienced concentrate users (N = 65, Female: 46%, 17 ± 11 days/month of concentrate use) were assessed for motor performance in a mobile laboratory before, immediately after, and 1 h after ad-libitum cannabis concentrate use. Plasma levels of THC were obtained via venipuncture at each timepoint. We used a remotely deployable motor performance battery to assess arm and leg movement speed, index finger tapping rate, and balance. The sensors on a smart device (iPod Touch) attached to the participant provided quantitative measures of movement. Results: Arm speed slowed immediately after concentrate use and remained impaired after 1 h (p < 0.001), leg speed slowed 1 h after use (p = 0.033), and balance decreased immediately after concentrate use (eyes open: p = 0.017, eyes closed: p = 0.013) but not at 1 h post-use. These effects were not different between sexes and there was no effect of concentrate use on finger tapping speed. Acute changes in THC plasma levels after use of concentrates were minimally correlated with acute changes in balance performance. Conclusions: Use of cannabis concentrates in frequent users impairs movement speed and balance similarly in men and women. The motor impairment is largely uncorrelated with the change in THC plasma levels. These results warrant further refinement of cannabis impairment testing and encourage caution related to use of cannabis concentrates in work and driving settings.

Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats.

RATIONALE: A challenge in treating substance use disorder is that successful treatment often does not persist, resulting in relapse and continued drug seeking. One approach to persistently weaken drug-seeking behaviors is to pair exposure to drug-associated cues or behaviors with delivery of a compound that may strengthen the inhibition of the association between drug cues and behavior. OBJECTIVES: We evaluated whether a selective histone deacetylase 3 (HDAC3) inhibitor could promote extinction and weaken contextual control of operant drug seeking after intravenous cocaine self-administration. METHODS: Male Long-Evans rats received a systemic injection of the HDAC3 inhibitor RGFP966 either before or immediately after the first extinction session. Persistence of extinction was tested over subsequent extinction sessions, as well as tests of reinstatement that included cue-induced reinstatement, contextual renewal, and cocaine-primed reinstatement. Additional extinction sessions occurred between each reinstatement test. We also evaluated effects of RGFP966 on performance and motivation during stable fixed ratio operant responding for cocaine and during a progressive ratio of reinforcement. RESULTS: RGFP966 administered before the first extinction session led to significantly less responding during subsequent extinction and reinstatement tests compared to vehicle-injected rats. Follow-up studies found that these effects were not likely due to a performance deficit or a change in motivation to self-administer cocaine, as injections of RGFP966 had no effect on stable responding during a fixed or progressive ratio schedule. In addition, RGFP966 administered just after the first extinction session had no effect during early extinction and reinstatement tests, but weakened long-term responding during later extinction sessions. CONCLUSIONS: These results suggest that a systemic injection of a selective HDAC3 inhibitor can enhance extinction and suppress reinstatement after cocaine self-administration. The finding that behavioral and pharmacological manipulations can be combined to decrease drug seeking provides further potential for treatment by epigenetic modulation.

Involvement of the dorsal hippocampus in expression and extinction of cocaine-induced conditioned place preference.

A key aspect of substance abuse is that drug taking often occurs in a specific context. As a consequence, exposure to drug-associated contexts can trigger cravings and relapse, even after long periods of abstinence. Although many studies have demonstrated that the hippocampus is critical for developing and retrieving contextual and spatial memories, comparatively little is known about the role of the hippocampus in acquiring and inhibiting memories involving contexts and drugs of abuse. We examined the effects of hippocampal inactivation on expression of cocaine-induced conditioned place preference (CPP) after initial acquisition or extinction of CPP in C57BL/6 mice. During acquisition of CPP, distinct tactile cues were paired with cocaine (20 mg kg-1 , intraperitoneal, CS+) and different tactile cues were paired with saline (CS-) on alternate days. Groups differed in whether the CS+ and CS- cues were presented in the same large space (one-compartment procedure) or distinct small spaces (two-compartment procedure), as previous findings demonstrate that a two-compartment configuration facilitates acquisition and attenuates extinction of a cocaine-induced CPP. Microinjection of the GABAA agonist, muscimol, into the dorsal hippocampus impaired (1) retrieval of a place preference after acquisition, (2) extinction of a place preference, and (3) retrieval of extinction. These effects differed depending on the spatial configuration during acquisition or extinction, suggesting that the dorsal hippocampus may differentially modulate drug seeking during retrieval and extinction of CPP.

Postural Steadiness and Ankle Force Variability in Peripheral Neuropathy.

INTRODUCTION: The purpose was to determine the effect of peripheral neuropathy (PN) on motor output variability for ankle muscles of older adults, and the relation between ankle motor variability and postural stability in PN patients. METHODS: Older adults with (O-PN) and without PN (O), and young adults (Y) underwent assessment of standing postural stability and ankle muscle force steadiness. RESULTS: O-PN displayed impaired ankle muscle force control and postural stability compared with O and Y groups. For O-PN, the amplitude of plantarflexor force fluctuations was moderately correlated with postural stability under no-vision conditions (r = .54, p = .01). DISCUSSION: The correlation of variations in ankle force with postural stability in PN suggests a contribution of ankle muscle dyscontrol to the postural instability that impacts physical function for older adults with PN.

Visuomotor Correction is a Robust Contributor to Force Variability During Index Finger Abduction by Older Adults.

We examined aging-related differences in the contribution of visuomotor correction to force fluctuations during index finger abduction via the analysis of two datasets from similar subjects. Study (1) Young (N = 27, 23 ± 8 years) and older adults (N = 14, 72 ± 9 years) underwent assessment of maximum voluntary contraction force (MVC) and force steadiness during constant-force (CF) index finger abduction (2.5, 30, 65% MVC). For each trial, visual feedback of the force (VIS) was provided for 8-10 s and removed for 8-10 s (NOVIS). Visual gain of the force feedback at 2.5% MVC was high; 12- and 26-fold greater than the 30 and 65% MVC targets. Mean force, standard deviation (SD) of force, and coefficient of variation (CV) of force was calculated for detrended (<0.5 Hz drift removed) VIS and NOVIS data segments. Study (2) A similar group of 14 older adults performed discrete, randomly-ordered VIS or NOVIS trials at low target forces (1-3% MVC) and high visual gain. Study (1) For young adults the CV of force was similar between VIS and NOVIS for the 2.5% (4.8 vs. 4.3%), 30% (3.2 vs. 3.2%) and 65% (3.5 vs. 4.2%) target forces. In contrast, for older adults the CV of force was greater for VIS than NOVIS for 2.5% MVC (6.6 vs. 4.2%, p < 0.001), but not for the 30% (2.4 vs. 2.4%) and 65% (3.1 vs. 3.3%) target forces. At 2.5% MVC, the increase in CV of force for VIS compared with NOVIS was significantly greater (age × visual condition p = 0.008) for older than young adults. Study (2) Similarly, for older adults performing discrete, randomly ordered trials the CV of force was greater for VIS than NOVIS (6.04 vs. 3.81%, p = 0.01). When visual force feedback was a dominant source of information at low forces, normalized force variability was ~58% greater for older adults, but only 11% greater for young adults. The significant effect of visual feedback for older adults was not dependent on the order of presentation of visual conditions. The results indicate that impaired processing of visuomotor information underlies the greater motor variability observed in older adults during lab-based isometric contractions of a hand muscle.

Histone-mediated epigenetics in addiction.

Many of the brain regions, neurotransmitter systems, and behavioral changes that occur after occasional drug use in healthy subjects and after chronic drug abuse in addicted patients are well characterized. An emerging literature suggests that epigenetic processes, those processes that regulate the accessibility of DNA to regulatory proteins within the nucleus, are keys to how addiction develops and how it may be treated. Investigations of the regulation of chromatin, the organizational system of DNA, by histone modification are leading to a new understanding of the cellular and behavioral alterations that occur after drug use. We will describe how, when, and where histone tails are modified and how some of the most recognized histone regulation patterns are involved in the cycle of addiction, including initial and chronic drug intake, withdrawal, abstinence, and relapse. Finally, we consider how an approach that targets histone modifications may promote successful treatment.

Cue configuration effects in acquisition and extinction of a cocaine-induced place preference.

A pervasive finding in animal models of substance abuse is that associations form quickly between contexts and drugs of abuse, such as cocaine. Studies of conditioned place preference (CPP) demonstrate that animals approach cues previously paired with cocaine. This is a commonly used preparation, but the configuration of the CPP apparatus differs across laboratories. Two common apparatus configurations for CPP are one compartment (in which the animal has access to the entire apparatus and spatial cues are irrelevant) or two compartments (in which access is restricted to one half of the apparatus and spatial cues are relevant). We compared the effects of acquisition and extinction of cocaine-induced CPP as a function of configuration. During CPP acquisition, C57BL/6J mice received cocaine paired with one tactile floor (conditioned stimulus; CS+) and saline paired with the other (CS-). CS+ and CS- trials occurred on alternate days in one of three configurations: one-compartment (exposure to the entire apparatus during CS+ or CS-), two-compartment consistent position (exposure to CS+ or CS- in adjacent, spatially distinct compartments), or two-compartment alternating position (exposure to CS+ or CS- in adjacent compartments that alternated spatial locations across days). A stronger preference for the CS+ floor occurred in two- versus one-compartment groups, with the strongest preference observed when cocaine was paired with alternating chamber positions. In contrast, greater loss of preference occurred after extinction in a one-compartment procedure, regardless of one- or two-compartment acquisition history. These findings suggest that a two-compartment configuration facilitated acquisition but attenuated extinction of a cocaine-induced CPP. The use of different CPP configurations may distinguish the underlying substrates and relevant cues for acquisition and extinction processes in cocaine abuse.

Comparative distribution of central neuropeptide Y (NPY) in the prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) vole.

Neuropeptide Y (NPY) has been implicated as a modulator of social behavior, often in a species-specific manner. Comparative studies of closely related vole species are particularly useful for identifying neural systems involved in social behaviors in both voles and humans. In the present study, immunohistochemistry was performed to compare NPY-like immunoreactivity (-ir) in brain tissue of the socially monogamous prairie vole and non-monogamous meadow vole. Species differences in NPY-ir were observed in a number of regions including the cortex, extended amygdala, septal area, suprachiasmatic nucleus, and intergeniculate leaf. Meadow voles had higher NPY-ir in all these regions as compared to prairie voles. No differences were observed in the striatum or hippocampus. The extended amygdala and lateral septum are regions that play a key role in regulation of monogamous behaviors such as pair bonding and paternal care. The present study suggests NPY in these regions may be an additional modulator of these species-specific social behaviors. Meadow voles had moderately higher NPY-ir in a number of hypothalamic regions, especially in the suprachiasmatic nucleus. Meadow voles also had much higher levels of NPY-ir in the intergeniculate leaflet, another key region in the regulation of circadian rhythms. Overall, species differences in NPY-ir were observed in a number of brain regions implicated in emotion, stress, circadian, and social behaviors. These findings provide additional support for a role for the NPY system in species-typical social behaviors.