The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

OBJECTIVE: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. METHODS: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. RESULTS: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. CONCLUSIONS: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Blended smartphone intervention for patients in opioid maintenance treatment in Iran: protocol for a randomized controlled trial.

BACKGROUND: The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms. OBJECTIVE: We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran. METHOD: Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models. DISCUSSION: This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT. TRIAL REGISTRATION: https://en.irct.ir/trial/53578 .

Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats.

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

A randomized controlled trial on the seeds of Sophora alopecuroides var. alopecuroides for the treatment of acute heroin withdrawal syndrome.

BACKGROUND: and purpose: The seeds of Sophora alopecuroides var. alopecuroides have attenuated the acute opium withdrawal syndrome in humans. Therefore, the efficacy and safety of a standardized extract of the plant for the treatment of acute heroin withdrawal syndrome was evaluated in abstinent heroin addicts. MATERIALS AND METHODS: The patients were randomized to take three 400 mg extract capsules (N = 50) or placebo (N = 50) once per day orally for eight days. The severity of withdrawal syndrome was assessed by the clinical opiate withdrawal scale (COWS) as the primary outcome measure at the baseline and on the days 3 and 8. The hepatic and renal functions and complete blood count were the secondary outcome measures tested at the baseline and end of the study. RESULTS: The COWS score decreased in both groups after eight days, but the decrease was significantly higher in the experimental group (p < 0.001); the effect size of the decrease was 2.64. The groups had significant differences in the COWS scores on the days 3 and 8 (p < 0.001 for both). The extract had no significant effect on the other parameters. No side effect was noted. CONCLUSION: The extract seems to alleviate acute heroin withdrawal syndrome safely.

Substance of choice, impact of heroin or opium on treatment retention in a multicentre randomised controlled trial in Iran.

INTRODUCTION: In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment. METHODS: Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted. RESULTS: Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm. DISCUSSION AND CONCLUSIONS: Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning.

The Lived Experience of Postpartum Women Attending Outpatient Substance Treatment for Opioid or Heroin Use.

INTRODUCTION: The current opioid crisis and associated heroin epidemic have exhausted the limited community services that are available to substance users, with only about 12% of substance use treatment facilities offering special programs for pregnant women. Little information is known about the lived experience of postpartum women in outpatient substance use treatment programs, who are working toward abstinence and caring for a newborn. The purpose of this phenomenological study was to explore the lived experience of postpartum women attending outpatient substance use treatment for illicit opioid or heroin use. METHODS: Individual interviews were conducted between December 2017 and November 2018, with 10 postpartum women with opioid use disorder (OUD) engaged in outpatient substance use treatment programs. A 4-step conceptual framework as suggested by Moustakas was used to understand and synthesize the lived experiences shared by the women. RESULTS: Five themes emerged from the raw data: the presence of a stigma in providers of health care services, a fear of being reported to family services, children are primary motivators to remain engaged in treatment, concern for the welfare of the infant, and barriers to treatment. DISCUSSION: Postpartum women with OUD and their infants have complex needs that may best be served by treatment programs that offer comprehensive care. The fear of being reported to family services and possible loss of custody influenced all aspects of their decision-making.

Building healthcare provider relationships for patient-centered care: A qualitative study of the experiences of people receiving injectable opioid agonist treatment.

BACKGROUND: Injectable opioid agonist treatment (iOAT) was designed as a pragmatic and compassionate approach for people who have not benefitted from medication assisted treatment with oral opioids (e.g., methadone). While, a substantial body of clinical trial evidence has demonstrated the safety and effectiveness of iOAT, considerably less is known about the patient-centered aspects of this treatment and their role in self-reported treatment goals and outcomes. The aim of this study was to explore participants' experiences in iOAT as they broadly relate to the domains of patient-centered care. A secondary goal was to explore how these experiences affected participants' self-reported treatment outcomes. METHODS: A qualitative methodology, and constructivist grounded theory approach, was used to guide sampling, data collection and analysis. A total of 30 in-depth interviews were conducted with people receiving iOAT in North America's first clinic. Audio-recordings for each semi-structured interview were transcribed and read repeatedly. The strategy of constant comparison was used through iterative stages of line-by-line, focused and theoretical coding until theoretical saturation was achieved. RESULTS: "Building healthcare provider relationships for patient-centered care in iOAT" was the emergent core concept. Healthcare provider relationships were established through two interrelated processes: 'Opening up' was attributed to the positive environment, and to feeling understood and supported by healthcare providers. 'Being a part of care' emerged as participants felt safe to ask for what was needed and had opportunities to collaborate in treatment decisions. These processes established a foundation in which participants experienced care that was responsive to their individual dose, health and psychosocial needs. CONCLUSIONS: The core concept suggested that therapeutic relationships were fundamental to experiences of patient-centered care in iOAT. When relationships were respectful and understanding, participants received individualized and holistic care in iOAT. These findings offer a valuable example of how therapeutic relationships can be strengthened in other substance use treatment settings, particularly when responding to the diverse treatment needs of clients.

Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction.

La captación de pacientes para el proyecto experimental de prescripción de estupefacientes de Andalucía (PEPSA): el papel del mediador / Patient recruitment for the experimental stupefacient prescription project in Andalusia (Spain): the role of the mediator

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Consigning "brutacaine" to history: a survey of pharmacological techniques to facilitate painful procedures in children in emergency departments in the UK.

OBJECTIVE: To determine the proportion of emergency departments in the UK that use modern pharmacological methods of pain and anxiety control in children, such as analgesia with intranasal diamorphine, procedural sedation using ketamine or midazolam, and adrenaline-cocaine gel, TAC or LAT for anaesthetising wounds in children. METHODS: A survey UK Emergency Departments conducted by email, post and telephone. RESULTS: Of the 183 (70%) of UK Emergency Departments responding, sedation is achieved using ketamine in 27% and using midazolam in 54%. In 55% of emergency departments intranasal diamorphine is used for analgesia and 41% use at least one of the topical local-anaesthetic mixtures to anaesthetise wounds before suturing. CONCLUSIONS: About half of UK emergency departments use modern pharmacological methods of procedural pain control in children. There is still considerable potential to improve the management of pain in children.

Methadone and heroin prescription: babies and bath water.

Criticism of methadone treatment abounds in all countries where this intervention is available. Although such criticism is often justified, it is critical to recognize that methadone is the most effective, safe, and cost-effective intervention available, is supported by innumerable studies, and provides considerable benefit to drug users, their families and communities. The major causes of the pervasive deficiencies of methadone treatment is the severe and consistent under-funding and hostile environment, both inevitable by-products of the global commitment over recent decades to an expensive, ineffective, and often counter-productive drug policy overly reliant on supply reduction. Methadone treatment is often criticized by drug war supporters not because of its limitations, but because its very effectiveness highlights the meagre benefits of supply reduction. The compelling arguments to expand pharmacotherapies for heroin dependence by rigorously evaluating prescription heroin treatment should not be based on the real or perceived deficiencies of methadone treatment. Rather, these arguments should be based on the need to provide evidence-based treatment for drug users which has the capacity, range of options, and quality expected in other health care services. The paramount aim should be to improve the current deplorable rates of death, disease, crime, and severe distress now evident in an increasing number of countries.

Myoclonic spasms following intrathecal diamorphine.

The use of intrathecal diamorphine via an implanted portal system is described for pain control in a patient suffering from vertebral metastatic disease. The complication of myoclonic spasms affecting the lower half of the body occurred after 14 days, when increasing the bolus dose to 40 mg. The spasms lasted for 3 hr and then gradually subsided. Diamorphine was subsequently restarted at a lower dose of 15 mg twice daily. On increasing the dose to 20 mg diamorphine 10 days later, severe distressing myoclonic spasms recurred 20 min postinjection. Myoclonus could only be controlled by instituting a local anesthetic intrathecal block. The patient was finally managed with 20 mg diamorphine per day by intrathecal infusion, and the pain was reasonably well controlled for the following 10 weeks without any recurrence of myoclonic spasms.

The therapeutic use of heroin: a review of the pharmacological literature.

Heroin is currently being advocated by some as a superior therapeutic agent for use in terminal illness. However, a review of the literature on heroin presently available does not support this contention. Administered orally, heroin is approximately 1.5 times more potent than morphine in controlling chronic pain in terminal cancer patients. Its effects on mood and the incidence and nature of side effects do not differ from those of morphine except in males where poorer pain control probably accounts for the worse effect on mood. Given parenterally for acute pain, heroin is 2-4 times more potent than morphine and faster in onset of action. When the potency difference is accounted for, the pharmacological effects of heroin do not differ appreciably from those of morphine. Heroin is metabolized to 6-acetylmorphine and morphine. After oral administration of heroin, morphine but not heroin or 6-acetylmorphine is detected in blood. In this case, heroin is a prodrug for the delivery of systemic morphine. Following acute i.v. administration, heroin appears transiently in blood with a half-life of about 3 min. The half-life of heroin exposed to blood or serum in vitro is 9-22 min, indicating that organ metabolism is involved in blood clearance as well. Direct renal clearance of heroin is less than 1% of the administered dose. In animal studies, heroin and 6-acetylmorphine are both more potent and faster acting than morphine as analgesics, effects attributed to their greater lipid solubility and subsequent penetration of the blood-brain barrier. Given centrally, morphine is more potent than heroin and 6-acetylmorphine in producing analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Extradural diamorphine in the control of pain following lumbar laminectomy.

Catheters were inserted into the extradural space under direct vision at the time of surgery for prolapsed intervertebral disc or lumbar canal stenosis. In the post-operative period, diamorphine (3 mg in 5 ml water) was injected through the catheter when patients requested analgesia. In only four of 49 patients was significant pain relief not achieved after extradural diamorphine injection. In four other patients it was not possible to use this method of analgesia throughout the two post-operative days as planned. As judged by the improved mobility and by grading on a linear analogue pain scale, the quality of analgesia achieved was better than after intramuscular papaveretum (10-20 mg) and extradural diamorphine was requested less frequently. There were no serious side-effects in the patients studied, although the technique was not used in patients over 55 years of age. Extradural diamorphine appeared to be less effective in two patients who had undergone re-explorations.