Phenibutan-an Illegal Food Supplement With Psychotropic Effects and Health Risks.

BACKGROUND: Phenibut (ß-phenyl-γ-aminobutyric acid) is an analog of the neurotransmitter gamma-aminobutyric acid (GABA). Like abapentin and pregabalin, it inhibits α2-δ-subunits of voltagedependent presynaptic calcium channels. The potential harm resulting from the use of these gabapentinoids is currently a matter of debate. METHODS: This review is based on pertinent publications retrieved by a selective literature search and on cases reported to the Giftinformationszentrum-Nord (GIZ-Nord), a poison information center at the University of Göttingen, Germany. RESULTS: Phenibut is a prescription drug in Russia but its production, possession, use, trafficking, or administration is illegal in Germany. The phenibut toxicity syndrome resembles that of gabapentinoids and GABA mimetics: benzodiazepine-like with - drawal symptoms including epileptic seizures, delirium and paradoxical activation have been described, as have cases of abuse and dependence. A few cases of use in the setting of multidrug abuse, and of phenibut-related death, have been described to date in the USA. The GIZ-Nord received 17 inquiries about phenibut, 55 about gabapentin, and 126 about pregabalin over the period 2008-2022. Over the same period, the GIZ-Nord was informed of 1207 cases involving Z substances and 4324 involving benzodiazepines. In the majority of the registered intoxications, including those with phenibut, the symptoms were mild. Overdoses of phenibut (2-100 g) were reported in 15 of the 17 cases; 8 of the persons who had taken an overdose were somnolent. In such cases, observation in intensive care was recommended. Respiratory depression or coma was not encountered in any case, not even in the patient who had taken 100 g of phenibut. CONCLUSION: Phenibut causes symptoms resembling those of gabapentinoid and benzodiazepine use. There have been reports of phenibut use in combination with other psychotropic drugs; in particular, its use together with opiates could increase the risk of coma and respiratory depression. No deaths due to phenibut intoxication have been published in Germany or elsewhere in Western Europe, although such cases may have been overlooked, as this drug is still largely unknown to Western medicine.

Effectiveness of Medical Cannabis for the Treatment of Depression: A Naturalistic Outpatient Study.

BACKGROUND: There is a lack of studies on the course and effectiveness of medical cannabis in the treatment of major depressive disorder (MDD). METHODS: Retrospective longitudinal (18 weeks) study of n=59 outpatients with MDD, treated with medical cannabis via a telemedical platform. Previous treatment with antidepressant medication was required for inclusion into the study. Standardized data collection was carried out at entry and during monthly consultations. Severity of depression was measured on a 0-10 point rating scale. Side-effects were assessed by a checklist. RESULTS: Patients were 20-54 years old; 72.9% were male; one third reported times of regular cannabis consumption within the previous five years. Drop-out rate was 22% after 18 weeks. Mean severity of depression decreased from 6.9 points (SD 1.5) at entry to 3.8 points (2.7) at week 18 (baseline observation carried forward; 95% CI for the mean difference: 2.4 to 3.8; p<0.001). A treatment response (>50% reduction of the initial score) was seen in 50.8% at week 18. One third of patients complained about side effects, none was considered as severe. Concomitant antidepressant medication (31% of patients) was not associated with outcome. CONCLUSIONS: Medical cannabis was well tolerated and dropout rate was comparable to those in clinical trials of antidepressant medication. Patients reported a clinically significant reduction of depression severity. Further research on the effectiveness of medical cannabis for MDD seems warranted. Risks of this medication, such as sustaining or inducing a cannabis use disorder, or side effects such as poor concentration, must be taken into consideration.

Further evidence of relationship between thiamine blood level and cognition in chronic alcohol-dependent adults: Prospective Pilot Study of an inpatient detoxification with oral supplementation protocol.

BACKGROUND: The relationship between thiamine blood level (TBL) and cognition remains uncertain, including among alcohol-dependent persons (ADP). AIM: To evaluate this relationship during protocol-driven inpatient alcohol detoxification treatment including thiamine supplementation (AD + Th). METHODS: Prospective 3-week study with 100 consecutively admitted detoxification-seeking ADP (47.7 ± 11 years old, 21% females) without superseding comorbidities requiring treatment. TBL and Montreal Cognitive Assessment (MoCA) were measured at admission (t1, pre-AD + Th) and discharge (t3, post-AD + Th). Frontal Assessment Battery (FAB) was performed at t1. AD + Th included abstinence, pharmacological alcohol withdrawal syndrome treatment, and oral thiamine supplementation (200 mg/day for 14 days). Regression and mediation analyses assessed TBL-cognition relationships. RESULTS: We found no cases of Wernicke Encephalopathy (WE) and only one case of thiamine deficiency. Both MoCA and TBL significantly improved across AD + Th (with medium-to-large effect sizes). At t1, TBL significantly predicted MoCA and FAB sum scores (medium effect sizes; extreme and very strong evidence, respectively). The clear TBL-MoCA association disappeared at t3. In multivariate regression and mediation analyses exploring key influential factors of cognition (identified by LASSO regression), the TBL-MoCA interactions did not relevantly change at t1 and t3. Age, serum transaminases, vitamin D levels, drinking-years, and depression score weakly modified the relationship. CONCLUSION: TBL was a robust predictor of pre-detoxification cognitive impairment, and both TBL and cognition improved significantly during AD + Th (including abstinence) in our ADP population, supporting routine thiamine supplementation for ADP, even those at low WE-risk. The TBL-cognition relationship was minimally confounded by age, alcohol-toxicity proxies, mood, and vitamin D levels.

Cannabinoids in the Treatment of Cannabis Use Disorder: Systematic Review of Randomized Controlled Trials.

Background: The prevalence of cannabis use and cannabis use disorders (CUD) has significantly increased over time. However, there are no approved pharmacological treatments for CUD. The aim of this study was to determine the efficacy and safety of various medical cannabinoids in the treatment of CUD. Methods: We conducted a systematic review of randomized controlled trials which evaluated the therapeutic potential of medical cannabinoids in individuals with CUD and summarized the main study outcomes in terms of cannabis use, abstinence, withdrawal symptoms, craving, retention in treatment and adverse events. Results: We identified eight trials with a total of 667 study participants. Dronabinol reduced cannabis withdrawal symptoms whereas nabiximols, cannabidiol and PF-04457845, a fatty acid amide inhibitor, also reduced cannabis use and improved abstinence, compared to placebo. Nabilone failed to demonstrate efficacy in the treatment of CUD. All medications were well-tolerated. Conclusions: Cannabinoid receptor agonists, i.e., dronabinol and nabilone, showed only limited or no therapeutic potential in the treatment of CUD. In contrast, modulators of endocannabinoid activity, i.e., nabiximols, cannabidiol and PF-04457845, demonstrated broader efficacy which covered almost all aspects of CUD. Endocannabinoid modulation appears to be a promising treatment approach in CUD, but the evidence to support this strategy is still small and future research in this direction is needed.

New Access Routes to Undertreated Populations; How Do Problem Substance Users Recruited from an Unemployment Office Differ from Detoxification Treatment Inpatients?

BACKGROUND: Only a minority of subjects with substance use disorders (SUDs) are in addiction-specific treatment (treatment gap). Co-operation between an unemployment office and a psychiatric hospital was established for the assessment and counseling of long-term unemployed clients with SUD. We aim at validating whether such a treatment gap exists in that group, and whether clients from an unemployment office differed from a matched group of inpatient detoxification patients with regard to socio-economic characteristics, substance use and treatment history, and the prevalence of mental disorders Methods: Unemployment office clients (n = 166) with an SUD were assessed using a standardized sociodemographic and clinical interview. They were compared with 83 inpatients from a local detoxification ward, matched for age, sex, and primary addictive disorder (matching ratio 2:1). RESULTS: Most (75.9%) subjects were males, with an average age of 36.7 years. The SUDs mostly related to alcohol (63.9%) and cannabis (27.7%). Although most unemployment office clients had a long SUD history, only half of them had ever been in addiction-specific treatment during their lifetime, and only one in four during the last year. There were no statistically significant differences between the groups regarding age at onset of problematic substance use, the proportion of migrants, and prevalence of comorbid mental disorders. The unemployment office sample showed lower levels of education (p < 0.001), job experience (p = 0.009), and current employment rates (p < 0.001). Conversely, inpatients showed lower rates of imprisonment (p < 0.001), more inpatient detoxification episodes (p < 0.03); and longer abstinence periods (p < 0.005). CONCLUSIONS: There was a lifetime and recent treatment gap in the group of long-term unemployed subjects with alcohol and cannabis dependence. The markedly lower educational attainment, chronic employment problems and higher degree of legal conflicts in the client group, as compared with patients in detoxification treatment, might require specific access and treatment options. The co-operation between the psychiatric unit and the unemployment office facilitated access to that group.

Prevalence of Novel Psychoactive Substance (NPS) Use in Patients Admitted to Drug Detoxification Treatment.

BACKGROUND: About 15 years ago, a diverse group of new recreational psychotropic substances began to emerge, which were marketed for example as "legal highs," "research chemicals," or "designer drugs." These substances were later subsumed under the label "Novel Psychoactive Substances" (NPS). Important NPS classes are cathinones, synthetic cannabimimetics, phenethylamines, and herbal drugs. The health care system for psychotropic substance use disorders (SUDs) traditionally focused on a few substances, such as alcohol, heroin, cocaine, amphetamines, or cannabis. Users of illicit substances often engage in polydrug use. However little is known about the prevalence of NPS use within the group of "classical" illicit substance users. OBJECTIVE: We investigated lifetime and recent use of NPS and other drugs in patients who underwent in-patient detoxification treatment from illicit drugs in Germany. METHODS: In a multicenter study with eight participating facilities, patients admitted to treatment underwent a standardized interview at admission, concerning their past and current substance use. The interview comprised classical substances of abuse, NPS, and rarely used substances such as LSD. In addition, participating sites had the opportunity to analyze their patients' routine drug screenings by means of gas chromatography/mass spectrometry (GC/MS), which permitted detection of NPS. RESULTS: Interviews from 295 patients could be analyzed. Most patients were opiate dependent and multiple substance users. About 32% reported use of synthetic cannabimimetics during lifetime, but usually only a few times. An important reason for their use was that NPS were not detected by drug testing in prisons or drug treatment facilities. Cathinones, herbal drugs or other NPS had rarely been used during lifetime. NPS use during the last 30 days before admission was nearly zero. This was confirmed by urine analysis results. In contrast, lifetime and current use of opiates, alcohol, cocaine, benzodiazepines, and cannabis was high. In addition, 18% reported of regular unprescribed pregabalin use during lifetime, and 20% had recently used pregabalin. CONCLUSION: Patients admitted to drug detoxification treatment showed multiple substance use, but this did not include NPS use. The diversion of legal medications such as pregabalin in this group is a serious concern.

Very Low Frequency of Drug Therapy of Alcohol Dependence in Germany - Analysis of Data of A Statutory Health Insurance.

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/-12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders.

[A short essay on the spirituality of placebo from an (evolutionary) psychiatric perspective]. / Ein kurzes Essay über die Spiritualität von Placebo aus (evolutionär) psychiatrischer Sicht.

Different to spirituality, the placebo-effect is well operationalized. Against this background, an attempt is made to look at a possible phenomenological relationship between the therapeutic effectiveness of spirituality and placebo. Similar context influences as well as the possible common use of a phylogenetically well conserved protective route via the mesolimbic dopaminergic reward system are highlighted. For both phenomena, the clinical effectiveness seems to be ubiquitous, with that of the placebo effect being scientifically much more verified than this currently would be methodologically possible with the "spirituality effect". Both effects share their uncertain predictability and are Janus-headed (e. g., placebo effect vs. nocebo effect). Currently, for both, the placebo and spirituality-oriented approaches, there are attempts underway to maximize their clinical effectiveness by modulating the therapeutic framework and conversational content. The discussion ends with the reflexive question of whether the placebo effect could have in essence "spirituality-light" traits.

New Psychoactive Substances (NPS) - a Challenge for the Addiction Treatment Services.

Over the last few years, hundreds of new psychoactive substances (NPS) have been identified in Europe. Apart from some herbal compounds, NPS mainly include synthetic cannabinoids and a range of new synthetic stimulants (e. g., cathinones). Synthetic NPS are often developed whilst modifying the basic chemical (e. g., phenethylamine or tryptamine) structure. Although the pharmacology and toxicology of most NPS are hardly known, they are being offered, especially online, as "bath salts," as "incense mixtures," or under other misleading labels. In addition, NPS are advertised as "legal highs," suggesting that, in contrast to substances regulated by the national laws, trading with NPS is legal. Although only little is known about the prevalence of NPS use, some of these molecules may be associated with a range of severe adverse reactions. Indeed, different from cannabis, synthetic cannabinoid users may present with epileptic seizures, loss of consciousness, and a range of persisting psychopathological disorders. Future studies should inform better-tailored management strategies.

[Frequent non-medical cannabis use: health sequelae and effectiveness of detoxification treatment]. / Häufiger Konsum von nicht-medizinischem Cannabis.

The non-medical (recreational) use of cannabis is common particularly among young adults. In light of the ongoing legalization debate the clinical impact of physical and psychosocial consequences of regular recreational cannabis consumption should be presented. Health consequences appear to be more pronounced the earlier the regular recreational cannabis use had been started in the individual's development. There is an increasing demand from recreational cannabis users for medical treatment of cannabis-related complaints including the cannabis withdrawal syndrome. Physical sequelae such as chronic bronchitis, cyclical hyperemesis and fertility problems are usually reversible along with abstinence. The often debilitating cannabis-related mental and cognitive complaints respond on a qualified inpatient detoxification treatment with high effect sizes (Cohen's d 0.7 -1.4). The severity of the cannabis addiction benefits sustainably from psychotherapeutic approaches and individual psychosocial counseling (Cohen's d 0,5-1,2). Currently, the actual health hazard of recreational cannabis use was evaluated by addiction experts to be significantly lower than that of tobacco or alcohol use.

Risks associated with the non-medicinal use of cannabis.

BACKGROUND: Cannabis is the most commonly consumed illicit drug around the world; in Germany, about 4.5% of all adults use it each year. Intense cannabis use is associated with health risks. Evidence-based treatments are available for health problems caused by cannabis use. METHODS: Selective literature review based on a search of the PubMed database, with special emphasis on systematic reviews, meta-analyses, cohort studies, randomized controlled trials (RCTs), case-control studies, and treatment guidelines. RESULTS: The delta-9-tetrahydrocannabinol content of cannabis products is rising around the world as a result of plant breeding, while cannabidiol, in contrast, is often no longer detectable. Various medical conditions can arise acutely after cannabis use, depending on the user's age, dose, frequency, mode and situation of use, and individual disposition; these include panic attacks, psychotic symptoms, deficient attention, impaired concentration, motor incoordination, and nausea. In particular, intense use of high doses of cannabis over many years, and the initiation of cannabis use in adolescence, can be associated with substance dependence (DSM-5; ICD-10), specific withdrawal symptoms, cognitive impairment, affective disorders, psychosis, anxiety disorders, and physical disease outside the brain (mainly respiratory and cardiovascular conditions). At present, the most effective way to treat cannabis dependence involves a combination of motivational encouragement, cognitive behavioral therapy, and contingency management (level 1a evidence). For adolescents, family therapy is also recommended (level 1a evidence). No pharmacological treatments can be recommended to date, as evidence for their efficacy is lacking. CONCLUSION: Further research is needed to elucidate the causal relationships between intense cannabis use and potential damage to physical and mental health. Health problems due to cannabis use can be effectively treated.

Longitudinal patterns of benzodiazepine consumption in a German cohort of methadone maintenance treatment patients.

OBJECTIVE: Cross-sectional studies show that considerable proportions of opiate dependents in methadone maintenance treatment (MMT) consume benzodiazepines (BZD). The longitudinal patterns of BZD use over time were described here. METHODS: After admission to MMT, patients from two outpatient MMT clinics (n = 345) were observed for up to 2 years whilst in treatment. The use of BZD, cannabis, opiates and cocaine was assessed by urine sampling carried out twice a month. RESULTS: For the whole sample, the mean BZD-positive urine specimen rate was 0.36 during the first 3 months. Rates slightly decreased during the first year and remained stable afterwards (last observation carried forward). For study completers (n = 152), the rate decreased over time, from 0.31 (first 3-month period) to 0.19 (last period; p < 0.001). According to a longitudinal cluster analysis, 26% of all patients showed a pattern of constantly high BZD-positivity rates, mostly in combination with other substances. Inpatient detoxifications from BZD (carried out in 18% of cases) did not have a sustained effect on levels of BZD use. CONCLUSIONS: BZD consumption in MMT is often part of a polydrug consumption pattern and is associated with poorer treatment retention. It is necessary to further investigate the reasons for BZD use in MMT patients and to develop effective interventions to reduce levels of BZD consumption.