Addiction Research Center Inventory Research Articles

Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study.

Objective: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have varying pharmacological actions with differential effects on acute and extended affective states, incuding anxiety. We aimed to study these effects on anxiety in legal market forms of cannabis. Method: This study makes use of a nonequivalent control group quasiexperimental design. Forty-two participants with anxiety symptions who were not using cannabis were compared to 258 participants with anxiety symptoms who used cannabis flower (∼3-4 times per week). Participants who used cannabis were randomly assigned to one of three legal market cannabis conditions; THC-dominant (24% THC, <1% CBD), THC+CBD (12% THC, 12% CBD), or CBD-dominant (<1% THC, 24% CBD). Changes in anxiety symptoms over 4-weeks were measured by the Patient Global Impression of Change (PGIC) scale and the Depression, Anxiety, and Stress Scale (DASS). Acute changes in subjective mood immediately after cannabis use were measured by the Profile of Mood States (POMS) Elation, Tension, and Paranoia subscales and the Addiction Research Center Inventory intoxication scale. Results: While all participants reported anxiety reductions over the 4-week study on the PGIC (F=30.65, p<0.001) and DASS anxiety measures (F=115.88, p<0.001), ad libitum CBD-dominant cannabis use was associated with lower scores on the DASS anxiety subscale compared to THC-dominant use when accounting for frequency of use (difference=-1.03, SE=0.45, p=0.02). Similarly, acute CBD-dominant cannabis use was associated with lower scores on the POMS tension and paranoia subscales (POMS tension: CBD-dominant vs. THC-dominant: difference=-0.41 SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.28, SE=0.07, p=0.04; POMS paranoia: CBD-dominant vs. THC-dominant: difference=-0.49, SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.33, SE=0.09, p=0.01). Participants in all cannabis conditions experienced acute changes in positive mood and subjective drug effects. Conclusions: This study provides novel information on the impacts of legal market cannabis with varying ratios of THC to CBD in indviduals with anxiety symptoms. Findings suggest that THC did not increase anxiety and that CBD-dominant forms of cannabis were associated with acute tension reduction that may translate to longer-term reductions in anxiety symptoms. Clinical Trial Registration: NCT03491384.

Responses to a "Typical" Morning Dose of Kratom in People Who Use Kratom Regularly: A Direct-Observation Study.

Use of kratom has outpaced systematic study of its effects, with most studies reliant on retrospective self-report. We aimed to assess acute effects following kratom use in adults who use regularly, and quantify alkaloids in the products, urine, and plasma. Between July and November 2022, 10 adults came to our clinic and orally self-administered their typical kratom dose; blinding procedures were not used. Physiological measures included blood pressure, respiratory rate, heart rate, pulse oximetry, temperature, and pupil diameter. Subjective outcomes included Subjective Opioid Withdrawal Scale, Addiction Research Center Inventory, and Drug Effects Questionnaire. Psychomotor performance was also assessed. Participants were 6 men and 4 women, mean age 41.2 years. Nine were non-Hispanic White; 1 was biracial. They had used kratom for 6.6 years (SD, 3.8 years) on average (2.0-14.1). Sessions were 190.89 minutes on average (SD, 15.10 minutes). Mean session dose was 5.16 g (median, 4.38 g; range, 1.1-10.9 g) leaf powder. Relative to baseline, physiological changes were minor. However, pupil diameter decreased (right, b = -0.70, P < 0.01; left, b = -0.73, P < 0.01) 40-80 minutes postdose and remained below baseline >160 minutes. Subjective Opioid Withdrawal Scale pre-dosing was mild (5.5 ± 3.3) and decreased postdose (b = [-4.0, -2.9], P < 0.01). Drug Effects Questionnaire "feeling effects" increased to 40/100 (SD, 30.5) within 40 minutes and remained above baseline 80 to 120 minutes (b = 19.0, P = 0.04), peaking at 72.7/100; 6 participants rated euphoria as mild on the Addiction Research Center Inventory Morphine-Benzedrine-scale. Psychomotor performance did not reliably improve or deteriorate postdosing. Among regular consumers, we found few clinically significant differences pre- and post-kratom dosing. Alkaloidal contents in products were within expected ranges.

Pharmacological effects of methylone and MDMA in humans.

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we aimed to evaluate the acute pharmacological effects of methylone and its abuse potential in humans when compared with that of MDMA following oral administration under controlled conditions. Seventeen participants of both sexes (14 males, 3 females) with a previous history of psychostimulant use completed a randomized, double-blind, placebo-controlled, crossover clinical trial. Participants received a single oral dose of 200mg of methylone, 100mg of MDMA, and a placebo. The variables included physiological effects (blood pressure, heart rate, oral temperature, pupil diameter), subjective effects using visual analog scales (VAS), the short form of the Addiction Research Center Inventory (ARCI), the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE), and the Sensitivity to Drug Reinforcement Questionnaire (SDRQ), and psychomotor performance (Maddox wing, psychomotor vigilance task). We observed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects, such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone exhibited an effect profile similar to MDMA, with a faster overall onset and earlier disappearance of subjective effects. These results suggest that abuse potential of methylone is comparable to that of MDMA in humans. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05488171; Identifier: NCT05488171.

Separate and combined effects of alcohol and cannabis on mood, subjective experience, cognition and psychomotor performance: A randomized trial

Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19–29 years with recent history of binge drinking completed this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial. Participants received: placebo alcohol and placebo cannabis (<0.1% THC); alcohol (target breath alcohol content [BrAC] 80 mg/dL) and placebo cannabis; placebo alcohol and active cannabis (12.5% THC); and active alcohol and cannabis over four sessions. Profile of Mood States (POMS), Addiction Research Centre Inventory (ARCI), verbal free recall (VFR), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), and grooved pegboard (GPB) task were administered before and approximately 75 min after drinking alcohol (1 h after smoking cannabis ad libitum). Significant effects of condition were found for the POMS (Tension-Anxiety, Confusion) and ARCI (MBG, LSD, PCAG, Euphoria, Sedation), predominantly with greater increases emerging after cannabis or alcohol-cannabis combined relative to placebo. Significant effects were found for VFR (immediate total and delayed recall, percent retained), DSST (trials attempted, trials correct, reaction time), and GPB (non-dominant hand) predominantly with greater declines in performance after alcohol and alcohol-cannabis combined relative to placebo and/or cannabis. Cannabis appeared to affect mood and subjective experience, with minimal impact on cognitive performance. Alcohol appeared to impair cognitive and psychomotor performance, with minimal impact on mood and subjective experience. Acute effects of alcohol and cannabis combined were additive at most.

Analgesic Effects of Oxycodone in Combination With Risperidone or Ziprasidone: Results From a Pilot Randomized Controlled Trial in Healthy Volunteers.

Background and ObjectivesPatients taking opioids are at risk of developing dependence and possibly abuse. Given the role of the mesolimbic dopamine system in opioid reward, blocking dopamine D2 receptors should limit the abuse liability of opioid analgesics. This pilot study evaluates the analgesic efficacy of oxycodone combined with an atypical antipsychotic (dopamine D2 receptor antagonist).MethodsA randomized, double-blind, within-subjects, controlled trial in healthy volunteers was conducted at UT Health SA Pain Clinic. Fifteen volunteers with previous medical exposure to opioids were enrolled. Risperidone (2 mg) or ziprasidone (80 mg) in combination with oxycodone (5, 10, 15 mg) was administered. Pain intensity using the cold pressor test, Current Opioid Misuse Measure (COMM), Addiction Research Center Inventory (ARCI, opioid subscale), Drug likability with drug effects questionnaire (DEQ) were assessed.ResultsOxycodone produced dose dependent increases in thermal analgesia on the cold pressor test that was significant at 10 and 15 mg (t = 3.087, P = 0.017). The combination did not significantly alter thermal analgesia. There was no significant effect of the combination on the ARCI or the POMS.Discussion and ConclusionThe combination of an atypical antipsychotic with oxycodone does not alter analgesic response or increase the incidence of adverse effects when compared to oxycodone alone. Such information is critical for the development of drug combinations for the treatment of pain and provide the foundation for future studies of abuse potential in drug users.Scientific SignificanceThis intervention in chronic pain patients is unique because it utilizes FDA approved drugs in combination to reduce abuse liability. The first step, and aim of this study, is to confirm the drug combination does not interfere with analgesic efficacy. The next step is to examine the combination in recreational drug users to assess the potential to block the euphoric effects of oxycodone. Ultimately, if this combination is effective, this approach could be beneficial in management of chronic pain.

Acute Pharmacological Effects and Oral Fluid Concentrations of the Synthetic Cannabinoids JWH-122 and JWH-210 in Humans After Self-Administration: An Observational Study.

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.

A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure.

Simple SummaryMethylone is a synthetic cathinone that is usually used as a substitute for conventional psychostimulants, such as MDMA. Chemically, methylone is considered the β-keto analogue of MDMA, with which it presumably shares similar pharmacological effects. To date, the available data about the human pharmacology of methylone in humans are very scarce and are mainly derived from user experiences, published in internet forums or intoxication reports. Thus, an observational–naturalistic study was conducted to evaluate the acute pharmacological effects and determine biomarkers of exposure in oral fluid of methylone after oral self-administration in comparison to MDMA. Methylone induced the prototypical psychostimulant and empathogenic effects commonly associated with MDMA, although they were of lower intensity. Oral fluid concentrations of methylone can be considered a suitable biomarker of acute exposure, and oral fluid has been proven to be a useful biological matrix of detection.Considered the β-keto analogue of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-Methylenedioxymethcathinone (methylone) is a synthetic cathinone. Over the years, methylone has been used as a substitute for conventional psychostimulants, such as MDMA. To date, little is known about the human pharmacology of methylone; the only available information has been provided by surveys or published intoxication reports. In the present observational–naturalistic study, we evaluate the acute subjective and physiological effects of methylone after oral self-administration in comparison to MDMA in healthy poly-drug users. Fourteen participants (10 males, 4 females) selected their single oral doses of methylone from 100 to 300 mg (n = 8, mean dose 187.5 mg) or MDMA from 75 to 100 mg (n = 6, mean dose 87.5 mg) based on their experience. Study variables were assessed at 0, 1, 2, and 4 h (h) and included vital signs (non-invasive blood pressure, heart rate, cutaneous temperature) and subjective effects using visual analogue scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI) short form, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) questionnaire. Additionally, oral fluid concentrations of methylone and MDMA were determined. Acute pharmacological effects produced by methylone followed the prototypical psychostimulant and empathogenic profile associated with MDMA, although they were less intense. Methylone concentrations in oral fluid can be considered a useful biomarker to detect acute exposure in oral fluid. Oral fluid concentrations of MDMA and methylone peaked at 2 h and concentrations of MDMA were in the range of those previously described in controlled studies. Our results demonstrate that the potential abuse liability of methylone is similar to that of MDMA in recreational subjects.

Acute Pharmacological Effects and Oral Fluid Biomarkers of the Synthetic Cannabinoid UR-144 and THC in Recreational Users.

Simple SummaryUR-144 is a synthetic cannabinoid found in herbal incenses for recreational use as a substitute of cannabis. It is a cannabinoid receptor agonist with effects on the central nervous system similar to those of THC. Several cases of intoxication involving UR-144 consumption have been reported. An observational study was carried out to assess UR-144 acute pharmacological effects in comparison with cannabis measuring biomarkers of disposition in oral fluid. Both UR-144 and THC increased blood pressure and heart rate. THC induced stimulant-like and high effects significantly more than those of UR-144 and the two parent drugs could be measured in oral fluid as biomarkers of consumption within 3 h following smoking of the substance.Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.

Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans.

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100–200 mg; mean 150 mg) or intranasally (n = 5, 50–100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.

Acute Exercise Increases Pain Threshold And Subjective Psychoactive Mood State

Prescription pain medication can be addictive and have long-term health consequences. Alternative pain-relieving strategies are becoming increasingly sought after. Exercise is known to have a pain-relieving effect which is thought to be mediated through the dopaminergic system. PURPOSE: To examine the relationships between minimum pain threshold (MPT), exercise blood lactate (EBL), and the self-reported psychoactive effects of exercise based on questions from the Morphine-Benzedrine Group, Morphine and Excitement subscales of the Addiction Research Center Inventory (ARCI) following acute exercise in college aged students. METHODS: Twelve college aged students (age = 20.9 ± 0.5yr) underwent 5 minutes of light leg cycling as a warmup. Following the warmup, they cycled for 20 minutes at 8 METS with an additional 5-minute cooldown. Measurements were taken prior to exercise and just before the cool down. EBL was collected as a measure of relative exercise intensity. The MPT was measured using a Wagner “Pain Test” algometer on the extensor carpi radialis. Results were assessed using a Student’s T-Test. RESULTS: Following exercise the MPT was increased by 62.1% ± 2.8 (P<0.001). Women had a greater increase in MPT (25.7 ± 9.1%) relative to men (15.8 ± 9.4%; P<0.05). EBL increased from an average of 1.8 ± 0.6 mmol/L at baseline to 4.1 ± 0.7 mmol/L following exercise (P<0.01). There was a positive linear correlation between MPT and EBL (r2=0.59; P<0.05). Indicating greater EBL levels were related to increased MPT. Positive responses from the ARCI subscale increased by 27 ± 3.3% following exercise (P<0.05). There was no effect of sex nor EBL on positive responses on the ARCI. CONCLUSIONS: These data suggest moderate intensity exercise can increase MPT and to a greater extent in women. Further, MPT correlated with increased EBL indicating that greater relative exercise intensity may modulate a greater increase MPT. Moderate intensity exercise increased positive responses on the ARCI providing evidence that the dopaminergic system may drive changes to MPT. However, positive responses did not correlate to EBL which may suggest another variable may augment pain reduction with increased exercise intensity.

Retrospectively assessed subjective effects of initial opioid use differ between opioid misusers with opioid use disorder (OUD) and those who never progressed to OUD: Data from a pilot and a replication sample.

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N=14) and heroin-addicted individuals in treatment for OUD (N=15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N=25) and without OUD (N=25) who were assessed as part of an ongoing genetic study. We observed similar significant between-group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD.

Acute Effects of 2C-E in Humans: An Observational Study.

2,5-Dimethoxy-4-ethylphenethylamine (2C-E) is psychedelic phenylethylamine, with a chemical structure similar to mescaline, used as new psychoactive substance (NPS). It inhibits norepinephrine and serotonin uptake and, more relevant, acts as a partial agonist of the serotonin 2A (5-HT2A), 2B (5-HT2B), and (5-HT2C) receptors. Consumers have reported that 2C-E induces mild-moderate psychedelic effects, but its pharmacology in humans, including pharmacological effects and pharmacokinetics, have not yet studied. To assess the acute effects of 2C-E on physiological and subjective effects and evaluate its pharmacokinetics, an observational study was carried-out. Ten recreational users of psychedelics self-administered a single oral dose of 2C-E (6.5, 8, 10, 15, or 25 mg). Blood pressure and heart rate were evaluated at baseline, 2, 4, and 6 h post-administration. Three rating scales were administered to evaluate subjective effects: a set of Visual Analog Scales (VAS), the 49-item short form version of the Addiction Research Centre Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 2, 4, and 6 h after self-administration. To assess 2C-E concentrations oral fluid (saliva) was collected during 6 h. 2C-E induced primarily alterations in perceptions, hallucinations, and euphoric-mood. Saliva maximal concentrations were achieved 2 h after self-administration. Administration of oral 2C-E at recreational doses produces a group of psychedelic-like effects such to 2C-B and other serotonin-acting drugs.

Drug Abuse Research Trend Investigation with Text Mining.

Drug abuse poses great physical and psychological harm to humans, thereby attracting scholarly attention. It often requires experience and time for a researcher, just entering this field, to find an appropriate method to study drug abuse issue. It is crucial for researchers to rapidly understand the existing research on a particular topic and be able to propose an effective new research method. Text mining analysis has been widely applied in recent years, and this study integrated the text mining method into a review of drug abuse research. Through searches for keywords related to the drug abuse, all related publications were identified and downloaded from PubMed. After removing the duplicate and incomplete literature, the retained data were imported for analysis through text mining. A total of 19,843 papers were analyzed, and the text mining technique was used to search for keyword and questionnaire types. The results showed the associations between these questionnaires, with the top five being the Addiction Severity Index (16.44%), the Quality of Life survey (5.01%), the Beck Depression Inventory (3.24%), the Addiction Research Center Inventory (2.81%), and the Profile of Mood States (1.10%). Specifically, the Addiction Severity Index was most commonly used in combination with Quality of Life scales. In conclusion, association analysis is useful to extract core knowledge. Researchers can learn and visualize the latest research trend.

Mephedrone and Alcohol Interactions in Humans.

Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as outpatients in four experimental sessions in a double-blind, randomized, cross-over, and placebo-controlled clinical trial. Participants received a single oral dose of 200 mg of mephedrone plus 0.8 g/kg of alcohol (combination condition); 200 mg of mephedrone plus placebo alcohol (mephedrone condition); placebo mephedrone plus 0.8 g/kg of ethanol (alcohol condition); and placebo mephedrone plus placebo alcohol (placebo condition). Outcome variables included physiological (blood pressure, heart rate, temperature, and pupil diameter), psychomotor (Maddox wing), subjective (visual analogue scales, Addiction Research Center Inventory 49 item short form, and Valoración de los Efectos Subjetivos de Sustancias con Potencial de Abuso questionnaire), and pharmacokinetic parameters (mephedrone and ethanol concentrations). The study was registered in ClinicalTrials.gov, number NCT02294266. The mephedrone and alcohol combination produced an increase in the cardiovascular effects of mephedrone and induced a more intense feeling of euphoria and well-being in comparison to the two drugs alone. Mephedrone reduced the sedative effects produced by alcohol. These results are similar to those obtained when other psychostimulants such as amphetamines and 3,4-methylenedioxymethamphetamine are combined simultaneously with alcohol. The abuse liability of mephedrone combined with alcohol is greater than that induced by mephedrone alone.

Increasing Chocolate's Sugar Content Enhances Its Psychoactive Effects and Intake.

Chocolate elicits unique brain activity compared to other foods, activating similar brain regions and neurobiological substrates with potentially similar psychoactive effects as substances of abuse. We sought to determine the relationship between chocolate with varying combinations of its main constituents (sugar, cocoa, and fat) and its psychoactive effects. Participants consumed 5 g of a commercially available chocolate with increasing amounts of sugar (90% cocoa, 85% cocoa, 70% cocoa, and milk chocolates). After each chocolate sample, participants completed the Psychoactive Effects Questionnaire (PEQ). The PEQ consists of questions taken from the Morphine-Benzedrine Group (MBG), Morphine (M,) and Excitement (E) subscales of the Addiction Research Center Inventory. After all testing procedures, participants completed the Binge Eating Scale (BES) while left alone and allowed to eat as much as they wanted of each of the different chocolates. We found a measurable psychoactive dose–effect relationship with each incremental increase in the chocolate’s sugar content. The total number of positive responses and the number of positive responses on the E subscale began increasing after tasting the 90% cocoa chocolate, whereas the number of positive responses on the MBG and M subscales began increasing after tasting the 85% cocoa chocolate sample. We did not find a correlation between BES scores and the total amount of chocolate consumed or self-reported scores on the PEQ. These results suggest that each incremental increase in chocolate’s sugar content enhances its psychoactive effects. These results extend our understanding of chocolate’s appeal and unique ability to prompt an addictive-like eating response.

Acute Pharmacological Effects of 2C-B in Humans: An Observational Study.

2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenylethylamine derivative, structurally similar to mescaline. It is a serotonin 5-hydroxytryptamine-2A (5-HT2A), 5-hydroxytryptamine-2B (5-HT2B), and 5-hydroxytryptamine-2C (5-HT2C) receptor partial agonist used recreationally as a new psychoactive substance. It has been reported that 2C-B induces mild psychedelic effects, although its acute pharmacological effects and pharmacokinetics have not yet been fully studied in humans. An observational study was conducted to assess the acute subjective and physiological effects, as well as pharmacokinetics of 2C-B. Sixteen healthy, experienced drug users self-administered an oral dose of 2C-B (10, 15, or 20 mg). Vital signs (blood pressure and heart rate) were measured at baseline 1, 2, 3, 4, and 6 hours (h). Each participant completed subjective effects using three rating scales: the visual analog scale (VAS), the Addiction Research Centre Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 2–3 and 6 h after self-administration (maximum effects along 6 h), and the Hallucinogenic Rating Scale (maximum effects along 6 h). Oral fluid (saliva) was collected to assess 2C-B and cortisol concentrations during 24 h. Acute administration of 2C-B increased blood pressure and heart rate. Scores of scales related to euphoria increased (high, liking, and stimulated), and changes in perceptions (distances, colors, shapes, and lights) and different body feelings/surrounding were produced. Mild hallucinating effects were described in five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and 3 h after self-administration, respectively. Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.

Spanish version validation of the Marihuana Motives Measure in a drug-consuming adolescent sample.

Cannabis is the illicit drug mostly widely consumed by adolescents in Spain. The understanding of consumption motives is an important factor for intervention. In Spain, there are no available instruments for their evaluation, hence, the goal of this paper is to study the psychometric properties of the Marihuana Motives Measure (MMM) in a sample of adolescent consumers. Firstly, translation and back-translation was performed. A total of 228 adolescent consumers of cannabis were evaluated. Factorial analysis was conducted, and the reliability of the total scores and of each scale of the questionnaire was studied through Cronbach's alpha. Test-retest reliability was analyzed through interclass correlations. Validity evidence of the MMM was examined through correlations between current cannabis use, subjective consumption effects measured with the Addiction Research Center Inventory (ARCI), and personality measured with the Millon Adolescent Clinical Inventory (MACI). High reliability was observed in total score of the MMM (Cronbach α = .86), and high and moderate reliability for each of the five factors obtained in the factorial analysis of the MMM, Social = .82, Enhancement = .72, Coping = .83, Expansion = .74, and Conformity = .64. Significant correlations were also observed between cannabis consumption motives and subjective effects, and between consumption motives and personality. The Spanish version of the MMM shows a similar factorial structure as the one obtained by the original author, and its measures are reliable and valid for the study of cannabis consumption motives in adolescent consumer population.

Human abuse potential of brivaracetam in healthy recreational central nervous system depressant users

BackgroundBrivaracetam is a new antiepileptic drug indicated for adjunctive treatment of focal seizures in adults at a dose of 50–200mg/day taken in two equal doses. The objective of this study was to evaluate the abuse potential of brivaracetam compared with alprazolam (positive control), placebo, and levetiracetam. MethodsThis was a randomized, double-blind, triple-dummy, crossover study in healthy male and female recreational central nervous system (CNS) depressant users aged 18–55years, who could distinguish between the subjective effects of alprazolam 2mg and placebo. All participants received single doses of brivaracetam (50 [therapeutic dose], 200, 1000mg [supratherapeutic doses]), alprazolam (1.5, 3mg), placebo, and levetiracetam (4000mg) in random order each separated by 7–10days. Subjective Visual Analogue Scales (VAS) and Addiction Research Center Inventory (ARCI) scales were completed at intervals up to 24h postdose. Primary endpoints were Drug Liking (at this moment) VAS, Overall Drug Liking VAS, Feeling High VAS, and ARCI Pentobarbital Chlorpromazine Alcohol Group (PCAG, sedation) maximum effect (Emax). Maximum effect values on each scale were analyzed using a mixed-effect model (per protocol population, N=44). ResultsThe maximum effect for both alprazolam doses was significantly greater versus placebo for six designated endpoints, confirming study validity. Drug Liking (at this moment) VAS Emax was significantly lower for brivaracetam 50mg than alprazolam (both doses); there were no significant differences between brivaracetam 200mg and alprazolam (both doses), and brivaracetam 1000mg and alprazolam 1.5mg. Brivaracetam 1000mg (supratherapeutic single dose) had significantly higher Drug Liking (at this moment) VAS Emax than alprazolam 3mg. Overall, Drug Liking VAS Emax for brivaracetam 50 and 200mg was not significantly different from alprazolam (both doses). Brivaracetam 1000mg had significantly higher Overall Drug Liking VAS Emax than alprazolam 1.5mg, but was not significantly different from alprazolam 3mg. Feeling High VAS Emax was lower versus alprazolam with brivaracetam 50 and 200mg, while brivaracetam 1000mg was comparable with alprazolam (both doses). Addiction Research Center Inventory PCAG Emax for brivaracetam (all doses) was significantly lower than alprazolam (both doses). On the secondary/supportive endpoints, compared with alprazolam, brivaracetam had fewer positive effects (ARCI Morphine Benzedrine Group [euphoria]; Good Drug Effects VAS [50mg]) and fewer negative effects (Bad Drug Effects VAS; ARCI Lysergic Acid Diethylamide [dysphoria]). Brivaracetam was not significantly different from alprazolam for Take Drug Again VAS (50, 200mg). For most endpoints, brivaracetam (50–200mg) was not significantly different from levetiracetam (4000mg). ConclusionThis study in healthy recreational CNS depressant users showed that single doses of brivaracetam 50mg (therapeutic single dose) had lower sedative, positive, and negative drug effects than alprazolam, while brivaracetam 200 and 1000mg (supratherapeutic single doses) were more similar to alprazolam. The subjective profile of brivaracetam appeared to be similar to that of levetiracetam, but further evaluation using a range of levetiracetam doses would be needed to confirm similar abuse potential.

Sweet taste liking is associated with subjective response to amphetamine in women but not men.

Preference for sweet taste rewards has been linked to the propensity for drug use in both animals and humans. Here, we tested the association between sweet taste liking and sensitivity to amphetamine reward in healthy adults. We hypothesized that sweet likers would report greater euphoria and stimulation following D-amphetamine (20mg) compared to sweet dislikers. Men (n=36) and women (n=34) completed a sweet taste test in which they rated their liking of various concentrations of sucrose and filtered water (0.05, 0.10, 0.21, 0.42, and 0.83M). Participants who preferred the highest concentration were classified as "sweet likers." All others were classified as "sweet dislikers." They then completed four sessions in which they received D-amphetamine (20mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation on the Addiction Research Center Inventory (ARCI) at regular intervals. We conducted linear mixed effects models to examine relationships between sweet liking and drug-induced euphoria and stimulation. Sweet likers reported significantly greater amphetamine-induced euphoria than did sweet dislikers among women. By contrast, sweet liking was not associated with amphetamine response in men. No associations with stimulation were observed. The association between sweet preference and amphetamine response in women is consistent with animal studies linking sweet taste preference and drug reward and also fits with observations that individuals who use drugs show a preference for sweet tastes. Whether the sex difference is related to circulating hormones, or other variables, remains to be determined.

Internalizing and externalizing personality and subjective effects in a sample of adolescent cannabis users.

Cannabis is the illicit substance most widely used by adolescents. Certain personality traits such as impulsivity and sensation seeking, and the subjective effects experienced after substance use (e.g. euphoria or relaxation) have been identified as some of the main etiological factors of consumption. This study aims to categorize a sample of adolescent cannabis users based on their most dominant personality traits (internalizing and externalizing profile). Then, to make a comparison of both profiles considering a set of variables related to consumption, clinical severity and subjective effects experienced. From a cross-sectional design, 173 adolescents (104 men and 69 women) aged 13 to 18 asking for treatment for cannabis use disorder in an Addictive Behavior Unit (UCAD) from the hospital were recruited. For the assessment, an ad hoc protocol was employed to register consumption, the Millon Adolescent Clinical Inventory (MACI) and the Addiction Research Center Inventory (ARCI) 49-item short form were also administered. Factor analysis suggested a two-profile solution: Introverted, Inhibited, Doleful, Dramatizing (-), Egotistic (-), Self-demeaning and Borderline tendency scales composed the internalizing profile, and Submissive (-), Unruly, Forceful, Conforming (-) and Oppositional scales composed the externalizing profile. The comparative analysis showed that the internalizing profile has higher levels of clinical severity and more subjective effects reported than the externalizing profile. These results suggest the need to design specific intervention strategies for each profile.