David Newcombe

Validation of the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): report of results from the Australian site

The concurrent, construct, discriminative and predictive validity of the World Health Organizations Alcohol Substance Involvement Screening Test (ASSIST) were examined in an Australian sample. One hundred and fifty participants, recruited from drug treatment (n = 50) and primary health care (PHC) settings (n = 100), were administered a battery of instruments at baseline and a modified battery at 3 months. Measures included the ASSIST; the Addiction Severity Index-Lite (ASI-Lite); the Severity of Dependence Scale (SDS); the MINI International Neuropsychiatric Interview (MINI-Plus); the Rating of Injection Site Condition (RISC); the Drug Abuse Screening Test (DAST); the Alcohol Use Disorders Identification Test (AUDIT); the Revised Fagerstrom Tolerance Questionnaire (RTQ); and the Maudsely Addiction Profile (MAP). Concurrent validity was demonstrated by significant correlations between ASSIST scores and scores from the ASI-lite, SDS, AUDIT and DAST; and significantly greater ASSIST scores for those with diagnoses of abuse or dependence. Construct validity was established by significant correlations between ASSIST scores and measures of risk factors for the development of drug and alcohol problems. Participants diagnosed with attention deficit/hyperactivity disorder or antisocial personality disorder had significantly higher ASSIST scores than those not diagnosed as such. Discriminative validity was established by the capacity of the ASSIST to discriminate between substance use, abuse and dependence. ROC analysis was able to establish cut-off scores for an Australian sample, with suitable specificities and sensitivities for most substances. Predictive validity was demonstrated by similarity in ASSIST scores obtained at baseline and at follow-up. The findings demonstrated that the ASSIST is a valid screening test for psychoactive substance use in individuals who use a number of substances and have varying degrees of substance use.

A Randomized Controlled Trial of a Brief Intervention for Illicit Drugs Linked to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in clients recruited from primary health care settings in four countries

AIMSnThis study evaluated the effectiveness of a brief intervention (BI) for illicit drugs (cannabis, cocaine, amphetamine-type stimulants and opioids) linked to the World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ASSIST screens for problem or risky use of 10 psychoactive substances, producing a score for each substance that falls into either a low-, moderate- or high-risk category.nnnDESIGNnProspective, randomized controlled trial in which participants were either assigned to a 3-month waiting-list control condition or received brief motivational counselling lasting an average of 13.8 minutes for the drug receiving the highest ASSIST score.nnnSETTINGnPrimary health-care settings in four countries: Australia, Brazil, India and the United States.nnnPARTICIPANTSnA total of 731 males and females scoring within the moderate-risk range of the ASSIST for cannabis, cocaine, amphetamine-type stimulants or opioids.nnnMEASUREMENTSnASSIST-specific substance involvement scores for cannabis, stimulants or opioids and ASSIST total illicit substance involvement score at baseline and 3 months post-randomization.nnnFINDINGSnOmnibus analyses indicated that those receiving the BI had significantly reduced scores for all measures, compared with control participants. Country-specific analyses showed that, with the exception of the site in the United States, BI participants had significantly lower ASSIST total illicit substance involvement scores at follow-up compared with the control participants. The sites in India and Brazil demonstrated a very strong brief intervention effect for cannabis scores (P < 0.005 for both sites), as did the sites in Australia (P < 0.005) and Brazil (P < 0.01) for stimulant scores and the Indian site for opioid scores (P < 0.01).nnnCONCLUSIONSnThe Alcohol, Smoking and Substance Involvement Screening Test-linked brief intervention aimed at reducing illicit substance use and related risks is effective, at least in the short term, and the effect generalizes across countries.

The new psychoactive substances regime in New Zealand: A different approach to regulation

The New Zealand government has proposed a new psychoactive substances regime, which will place the onus onto manufacturers to prove that their products pose a low risk of harm, prior to receiving approval which allows the products to be legally manufactured and sold. This is an innovative and unique development in the regulation of emerging psychoactive substances, and offers an alternative response to prohibition. The details of the new regime and how it will operate are now emerging, and this offers an opportunity to critically explore some of the issues related to the proposed new regime and to speculate on some of the outcomes. This paper brings together a group of New Zealand based researchers from a range of disciplines with experience of ‘legal high’ research to discuss this innovative new regime.

Self‐Reported Risk‐Taking Behavior During Matched‐Frequency Sessions of Alcohol Versus Combined Alcohol and Energy Drinks Consumption: Does Co‐Ingestion Increase Risk‐Taking?

BACKGROUNDnEmerging evidence indicates that consumers of alcohol mixed with energy drink (AmED) self-report lower odds of risk-taking after consuming AmED versus alcohol alone. However, these studies have been criticized for failing to control for relative frequency of AmED versus alcohol-only consumption sessions. These studies also do not account for quantity of consumption and general alcohol-related risk-taking propensity. The aims of the present study were to (i) compare rates of risk-taking in AmED versus alcohol sessions among consumers with matched frequency of use and (ii) identify consumption and person characteristics associated with risk-taking behavior in AmED sessions.nnnMETHODSnData were extracted from 2 Australian community samples and 1 New Zealand community sample of AmED consumers (nxa0=xa01,291). One-fifth (21%; nxa0=xa0273) reported matched frequency of AmED and alcohol use.nnnRESULTSnThe majority (55%) of matched-frequency participants consumed AmED and alcohol monthly or less. The matched-frequency sample reported significantly lower odds of engaging in 18 of 25 assessed risk behaviors in AmED versus alcohol sessions. Similar rates of engagement were evident across session type for the remaining behaviors, the majority of which were low prevalence (reported by <15%). Regression modeling indicated that risk-taking in AmED sessions was primarily associated with risk-taking in alcohol sessions, with increased average energy drink (ED) intake associated with certain risk behaviors (e.g., being physically hurt, not using contraception, and driving while over the legal alcohol limit).nnnCONCLUSIONSnBivariate analyses from a matched-frequency sample align with past research showing lower odds of risk-taking behavior after AmED versus alcohol consumption for the same individuals. Multivariate analyses showed that risk-taking in alcohol sessions had the strongest association with risk-taking in AmED sessions. However, hypotheses of increased risk-taking post-AmED consumption were partly supported: Greater ED intake was associated with increased likelihood of specific behaviors, including drink-driving, sexual behavior, and aggressive behaviors in the matched-frequency sample after controlling for alcohol intake and risk-taking in alcohol sessions. These findings highlight the need to consider both personal characteristics and beverage effects in harm reduction strategies for AmED consumers.

Pharmacokinetics of cytisine, an α4β2 nicotinic receptor partial agonist, in healthy smokers following a single dose

Cytisine, an α4 β2 nicotinic receptor partial agonist, is a plant alkaloid that is commercially extracted for use as a smoking cessation medication. Despite its long history of use, there is very little understanding of the pharmacokinetics of cytisine. To date, no previous studies have reported cytisine concentrations in humans following its use as a smoking cessation agent. A high performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated for analysis of Tabex® and nicotine-free oral strips, two commercial products containing cytisine. A sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the quantification of cytisine in human plasma and for the detection of cytisine in urine. Single-dose pharmacokinetics of cytisine was studied in healthy smokers. Subjects received a single 3u2009mg oral dose administration of cytisine. Cytisine was detected in all plasma samples collected after administration, including 15u2009min post-dose and at 24u2009h. Cytisine was renally excreted and detected as an unchanged drug. No metabolites were detected in plasma or urine collected in the study. No adverse reactions were reported.

Regulating new psychoactive drugs: innovation leading to compromise

Owing to the increasing availability of new, and legal, psychoactive drugs (NPDs),1 the New Zealand government enacted ground breaking legislation in May 2013; the Psychoactive Substance Act requires evidence of low risk before NPDs can be legally sold.2 3 A transitional period was created until safety testing regimes were finalised. Public outrage, however, grew as adverse effects of “interim approved” drugs …

Illicit drug use among New Zealand gay and bisexual men: Prevalence and association with sexual health behaviours

INTRODUCTION AND AIMSnData are lacking on drug use among gay and bisexual men (GBM) in New Zealand. We establish a baseline estimate of drug use and investigate associations with sexual health and HIV risk.nnnDESIGN AND METHODSnA cross-sectional survey of GBM was conducted in gay community settings and online. Participants were asked their frequency of using nine drugs (poppers, cannabis, ecstasy, methamphetamine, amphetamine, cocaine, LSD, gamma hydroxybutyrate and ketamine) in the previous 6xa0months. We examined associations between selected drugs and number of recent partners, unprotected anal intercourse with a casual partner and sexually transmitted infections using adjusted odds ratios (AOR).nnnRESULTSnOverall, 3211 participants provided information of whom 55.8% reported any drug use, and 37.9% cannabis, 36.7% poppers, 16.5% ecstasy, 10.5% amphetamine, 7.4% methamphetamine, 6.6% LSD, 6.1% cocaine, 5.3% gamma hydroxybutyrate and 4.4% ketamine use. A quarter of all respondents (25.6%) reported using one drug, 22.8% two to four and 7.4% five or more drugs (polydrugs). Methamphetamine and polydrug use was independently predictive of reporting >20 recent partners (AOR 1.6 and 7.0, respectively), unprotected anal intercourse with a casual partner (AOR 1.8 and 3.2, respectively) and a sexually transmitted infection (AOR 1.6 and 4.3, respectively).nnnDISCUSSION AND CONCLUSIONSnDrug use was common in this sample of GBM. Polydrug and methamphetamine users had especially high sexual health needs, but risks remained elevated among GBM consuming other drugs. Drug harm reduction programs and HIV prevention should target GBM with problematic drug use. Limitations include an inability to attribute causation. [Saxton P, Newcombe D, Ahmed A, Dickson N, Hughes A. Illicit drug use among New Zealand gay and bisexual men: Prevalence and association with sexual health behaviours. Drug Alcohol Rev 2017;00:000-000].

The Effect of Varenicline Administration on Cannabis and Tobacco Use in Cannabis and Nicotine Dependent Individuals ? A Case-Series

Introduction: Cannabis users may also use tobacco products which increases the potential for drug-induced harm over and above that caused by one substance on its own. Therefore, a pharmacotherapy that treats dependence on both substances would be beneficial. Tetrahydrocannabinol and varenicline act at the α7 subtype of the nicotinic receptor and so it was hypothesised that varenicline may also effect cannabis use. nMethods: Five nicotine and cannabis dependent individuals (median age 37), who were attending a community alcohol and drug service, and who expressed a desire to quit tobacco smoking, were prescribed 12 weeks of varenicline and were followed up weekly for the first month, then fortnightly for as long as possible over this time. nResults: Four of the five cases reported reducing their use of both substances after commencing varenicline, and also of experiencing less enjoyment from using these substances. The remaining case withdrew early in the study due to a migraine. No participant reported taking varenicline for more than 6 weeks, and only one could be followed up for 12 weeks. The reasons reported by participants for ceasing varenicline included feeling flat, experiencing nausea and vomiting, feeling angry and being short tempered, and as a result of a variety of family stressors. nConclusion: The administration of varenicline to cannabis users was associated with reductions in the enjoyment reported from using cannabis, and the amount of cannabis used. These results support further investigation of varenicline’s potential as a therapeutic intervention to treat dependence on nicotine and cannabis.

Plasma concentrations of cytisine, a commercially available plant-based alkaloid, in healthy adult smokers taking recommended doses for smoking cessation

Abstract 1. Cytisine is a plant alkaloid that is a partial agonist for the α4β2 -nAChRs and is used as an aid to smoking cessation. To date, there are no published data on cytisine concentrations in humans following multiple dosing. The aim of this study was to determine cytisine plasma concentrations after taking recommended doses for smoking cessation and to report on adverse effects. 2. Subjects (n=10) were instructed to follow the 25-day standard dosing regimen of cytisine. Blood was collected at 0, 2, 4, 8 and 10 hours on day 1 then on subsequent visits (days 2, 3, 4, 6, 13, 14, 17, 18, 21, 22, 25 and 26) to measure plasma cytisine concentrations. Plasma concentrations were determined using a validated LC-MS method. 3. Accumulation of cytisine was observed with repeated dosing of cytisine on day 1. Mean ± SEM plasma cytisine concentration measured at 10 hours was 50.8u2009±u20094.7u2009ng/mL. Due to dose tapering, there was an overall decrease in plasma cytisine concentration over the whole treatment period. 4. Overall, cytisine was well-tolerated and adverse effects reported were minor, indicating that cytisine is safe at concentrations measured in this study. This study is registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12613000002785).

Ibogaine for treating drug dependence. What is a safe dose

The indole alkaloid ibogaine, present in the root bark of the West African rain forest shrub Tabernanthe iboga, has been adopted in the West as a treatment for drug dependence. Treatment of patients requires large doses of the alkaloid to cause hallucinations, an alleged integral part of the patients treatment regime. However, case reports and case series continue to describe evidences of ataxia, gastrointestinal distress, ventricular arrhythmias and sudden and unexplained deaths of patients undergoing treatment for drug dependence. High doses of ibogaine act on several classes of neurological receptors and transporters to achieve pharmacological responses associated with drug aversion; limited toxicology research suggests that intraperitoneal doses used to successfully treat rodents, for example, have also been shown to cause neuronal injury (purkinje cells) in the rat cerebellum. Limited research suggests lethality in rodents by the oral route can be achieved at approximately 263mg/kg body weight. To consider an appropriate and safe initial dose for humans, necessary safety factors need to be applied to the animal data; these would include factors such as intra- and inter-species variability and for susceptible people in a population (such as drug users). A calculated initial dose to treat patients could be approximated at 0.87mg/kg body weight, substantially lower than those presently being administered to treat drug users. Morbidities and mortalities will continue to occur unless practitioners reconsider doses being administered to their susceptible patients.