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Cardiovascular magnetic resonance (CMR) has emerged as a powerful tool with which to study atherosclerosis. In this chapter we describe how CMR can be used to accurately assess not only the amount of atherosclerotic plaque across multiple vascular beds but also the nature of that plaque providing a detailed soft tissue characterization to differentiate stable from unstable plaque phenotypes. Moreover, the assessment of atherosclerotic disease activity has also become possible with the emergence of targeted MR contrast agents and hybrid MR and positron emission tomography (PET) scanners. In combination, CMR therefore provides a versatile, comprehensive, and multiparametric assessment of atherosclerosis in humans, although further work is required to validate these approaches and to transfer them in to the coronary arteries.

Background Pulmonary tuberculosis (PTB) is a global health problem and remains the leading infectious cause of death worldwide. Differentiation between secondary PTB and non-tuberculous (non-TB) pneumonia is important for patient isolation and treatment, but can be difficult to determine clinically and radiologically. We proposed the application of deep learning to chest computerized tomography (CT) to assist doctors in detecting and differentiating PTB from non-TB pneumonia in an expedient, non-invasive, and reproducible manner. Methods: We retrospectively collected a dataset containing 1,124 CT scans from 923 PTB and non-TB pneumonia based on their pathological reports of lung biopsy and clinical information and 201 patients without pulmonary infiltrate from West China Hospital between 2012 and 2018. Randomly selected parts of this dataset (WCPR dataset) were used to develop, train, internally validate and test the algorithm. Patients in the WCPR dataset (PTB, n=439; non-TB pneumonia, n=484; normal, n= 201) were randomly assigned in three non-overlapping sets: training set, n=866; validation set, n=108; and test set, n=150. An additional dataset from NIH TB Portal31 comprising of cases from three countries (Belarus, n = 274; Romania, n = 43; Moldova, n = 10) was used to validate externally the algorithm's ability to identify PTB. A convolutional neural network of Inception-Res-Net-v230 was trained and tested on the entire chest CT to mimic real life application. The performance of our algorithm was compared to three trained radiology/pulmonology physicians. Findings For differentiating pulmonary infiltrates, the algorithm achieved 99·3% accuracy (149 out of 150), 99.0% sensitivity, and 100·0% specificity. For identifying PTB, the algorithm achieved 82·0% accuracy (123 out of 150), 95·9% sensitivity, and 75·2% specificity. For identifying non-TB pneumonia, the algorithm achieved 81·3% accuracy (122 out of 150), 52·7% sensitivity, and 97·9% specificity. This mostly outperformed our human readers for PTB identification, who averaged up to 81·1% accuracy, 70·8% sensitivity, and 86·1% specificity. Our algorithm identified 287 out of 327 PTB (87·8% accuracy) cases in NIH TB Portal Dataset from other countries. Interpretation: Our deep-learning-based algorithm successfully differentiated abnormal from normal chest CTs, as well as PTB from non-TB pneumonia cases and thus allows real world applicability. Early identification of PTB from non-TB pneumonia can help control outbreaks through isolation and early appropriate treatment. The application of our algorithm could expedite the identification of PTB, thereby improving clinical outcomes. Our datasets and algorithm used in this study will be publicly available to facilitate world-wide adoption. Funding Statement: The authors declare: "None." Declaration of Interests: The authors declare: "None." Ethics Approval Statement: This study was approved by the Institutional Review Board of West China Hospital (approval No. 2019-148) and Icahn School of Medicine at Mount Sinai (approval No. GCO#1: 19-0569(0001) ISMMS), and the patients’ written consents were waived.

Approximately one third of patients diagnosed with schizophrenia do not achieve adequate symptom control with standard antipsychotic drugs (APs). Some of these may prove responsive to clozapine, but non-response to APs remains an important clinical problem and cause of increased health care costs. In a significant proportion of patients, schizophrenia is associated with natural and iatrogenic metabolic abnormalities (obesity, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus), hyperadrenalism and an exaggerated HPA response to stress, and chronic systemic inflammation. The endocannabinoid system (ECS) in the brain plays an important role in maintaining normal mental health. ECS modulates emotion, reward processing, sleep regulation, aversive memory extinction and HPA axis regulation. ECS overactivity contributes to visceral fat accumulation, insulin resistance and impaired energy expenditure. The cannabis plant synthesises a large number of pharmacologically active compounds unique to it known as phytocannabinoids. In contrast to the euphoric and pro-psychotic effects of delta-9-tetrahydrocannabinol (THC), certain non-intoxicating phytocannabinoids have emerged in pre-clinical and clinical models as potential APs. Since the likely mechanism of action does not rely upon dopamine D2 receptor antagonism, synergistic combinations with existing APs are plausible. The anti-inflammatory and immunomodulatory effects of the non-intoxicating phytocannabinoid cannabidiol (CBD) are well established and are summarised below. Preliminary data reviewed in this paper suggest that CBD in combination with a CB1 receptor neutral antagonist could not only augment the effects of standard APs but also target the metabolic, inflammatory and stress-related components of the schizophrenia phenotype. © 2014 Bentham Science Publishers.

There is a growing consensus that cannabis dependence is a substantial and underappreciated problem. The key component responsible for the euphoric effects of cannabis and its dependence potential is δ-9-tetrahydrocannabinol (THC). THC-containing cannabinoid medicines theoretically pose a risk of abuse and dependence.In order to evaluate the potential of Sativex to cause cannabis-like psychoactivity, abuse or dependence relevant data from all published papers have been reviewed along with the integrated safety analysis for Sativex use in multiple sclerosis (MS) patients on file at GW Pharmaceuticals.In clinical trials, intoxication scores have been low and euphoria reported by only 2.2% of patients. Tolerance has not occurred, abrupt withdrawal has not resulted in a formal withdrawal syndrome, and no cases of abuse or diversion have been reported to date. A formal abuse liability study of Sativex in experienced cannabis smokers showed some abuse potential in comparison with placebo at higher doses, but scores were consistently lower than equivalent doses of THC. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.

Background Both preclinical and human research suggest that cannabidiol (CBD) has antipsychotic properties. This study assessed the safety and effectiveness of CBD in patients with schizophrenia. Methods Patients with schizophrenia (n=88) were randomized to receive CBD (1000 mg/day) or placebo alongside their existing antipsychotic medication for 6 weeks. Participants were assessed before and after treatment using the PANSS, BACS, GAF scales, and the CGI Improvement and Severity scales. Results Compared those given placebo, patients treated with CBD had lower levels of positive psychotic symptoms (PANSS; p=0.02), and were more likely to have been rated by clinicians as improved (CGI-I; p=0.02) and as not severely unwell (CGI-S; p=0.04). Patients who received CBD also showed trends for greater improvements in cognitive performance (BACS; p=0.07) and in overall functioning (GAF; p=0.08). There was no difference in the frequency of CBD of adverse events between CBD and placebo. Discussion These data suggest that CBD has beneficial effects in patients with schizophrenia and is not associated with significant adverse effects.

Background: Interruption of supply of pharmaceutical opiates can cause major challenge to the continuity of management of opiate-dependent patients on maintenance treatment. Policy makers and practitioners need to learn lessons from the experiences of these occasional crises. Method: Through case report and clinical audit, we report on the opiate switch and dose conversion strategies with 14 patients previously receiving dextromoramide (Palfium®) as opiate addiction maintenance treatment. Results: Patients were switched to a wide range of different opiates, of which the most commonly-selected was morphine. Dose conversion ratios varied greatly between patients. Conclusion: Lessons need to be learnt from serendipitous experiments. In the absence of pre-existing guidance, great diversity of empirically derived practice occurred. Perhaps the most important lessons to be learnt are, first, that no rigid formula for conversion can be universally applied, second, that considerable between-subject variation will...

The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5- 120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient’s most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P- 0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.

SUMMARY This Phase I, open label, four-way crossover study pertains to pharmacokinetic parameters of four cannabis based medicine extracts (CBME). Sublingual, buccal and oro-pharyngeal test treatments (GW-1000-02) consisted of 25 mg cannabidiol (CBD) + 25 mg Δ9-tetra-hydrocannabinol (THC) per ml formulated in ethanol (eth):propylene glycol (PG) (50:50), with peppermint flavouring with a 100 μl actuation volume (total dose 10 mg CBD + 10 mg THC in 4 actuations). An oral capsule contained 2.5 mg CBD + 2.5 mg THC sprayed onto granulated lactose and encapsulated in soft gelatin capsules (total dose of 10 mg CBD + 10 mg THC 4 capsules). This study was performed in healthy volunteers in an open label, 4 period, 3-way randomised crossover followed by a nonrandomised oral dose using single doses of 20 mg of CBME (10 mg CBD + 10 mg THC). In Periods 1 to 3, the test treatment was administered as a liquid spray according to the randomisation scheme (i.e., sublingually, buccally, oro-pharyngeally). In Period 4 the te...

SUMMARY Primary objectives of this study were to assess the pharmacokinetic characteristics of CBME when administered sublingually in different ratios, to determine if the pharmacokinetic profiles of THC and its metabolite 11-hydroxy-THC are different when administered sublingually in different formulations, and to characterise the pharmacokinetic profile of CBD when administered with THC in equal amounts. Secondary objectives were to determine if there was a correlation between intoxication levels and plasma concentrations of THC and/or its metabolite 11-hydroxy-THC, and to assess safety and tolerability of CBME when administered sublingually. Methodology employed a double-blind, randomised, three-way crossover study of placebo, High THC and CBD:THC administered sublingually as a liquid spray. Twenty-four subjects were planned, dosed, completed the study and were analysed. Test products were Δ9-tetrahydrocannabinol (THC, formulated as 25 mg THC per ml) with or without cannabidiol (CBD) (formulated as 25 ...

To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Δ(9) -Tetrahydrocannabinol (Δ(9) -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and Δ(9) -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ(9) -THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ(9) -THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Cannabis is now emerging from a period of prohibition and being revisited as a potential source of treatments for conditions ill served by synthetic substances. Previous research focussed primarily on effects produced by synthetic cannabinoids such as THC, or cannabis of unknown cannabinoid content. Chemovars of cannabis characterized by high content of specific cannabinoids (primarily, but not only THC and CBD) have been developed. Clinical research using defined extracts from these chemovars is now underway in the UK. Many diseases are multifactorial; a variety of receptors need to be targeted to produce a therapeutic effect. A defined botanical may better achieve this than a single synthetic compound as the components can act synergistically. A new generation of cannabis based medicinal products takes advantage of increasing understanding of the mode of action of cannabinoids, evidence-based research on clinical uses and new technology for realization of products, in anti-diversionary presenta...

BackgroundReview commissioned in 1996 by the Department of Health (DOH).AimsAssess therapeutic profile of cannabis and cannabinoids.MethodMedline search, references supplied by DOH and others, and personal communications.Results and ConclusionsCannabis and some cannabinoids are effective antiemetics and analgesics and reduce intraocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

ABSTACT An anonymous questionnaire was sent to all the undergraduates in a single College within Oxford University in order to explore perceptions of university life, levels of stress and emotional well‐being, attitudes and beliefs about alcohol and drugs, and the pattern of use of these substances. The response rate was 76%. There was a high level of contentment with College life, but a third of students had felt rejected on grounds of social class, and a third of the women reported sexual discrimination or harassment. Average self esteem of the women equated to a control population, but that of the men was abnormally high. Promiscuous sexual behaviour was unusual. A third of the women reported at least one episode of problematic binge‐eating or dieting. Correlational analysis suggested the existence of a small minority of vulnerable, unhappy students. Drug and alcohol use among Oxford undergraduates approximates to that of a similar age group in the general population. A third of students consume more t...

The responses of ex-smokers to an experimental cue exposure trial, and the effect of caffeine on these responses, were compared with those of a matched group of control subjects in a placebo controlled single-blind cross-over design. In contrast to placebo, caffeine protected the ex-smokers from a surge of anxiety and rise in blood pressure associated with exposure to smoking-related cues. Caffeine had no significant effects on the control group at this dose (equivalent to a single cup of strong coffee). The results are discussed with reference to Stewart's conditioned appetitive motivational model of addiction. It is suggested that further work may identify caffeine as an adjunct to smoking relapse prevention measures.

Assertiveness training in groups drawn from the community and a psychiatric hospital is described. As an outcome marker, the self-esteem of these two samples was measured before and after the training, and at several months' follow-up, using a 30-item self-report questionnaire. For most participants, highly significant improvements in self-esteem were noted both at the end of the courses and at follow-up. The theoretical background to assertiveness training and a number of practical issues are discussed.

Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21- 814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five ‘serious adverse events’ between them - two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of - tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.

Objectives. To assess the efficacy of a cannabis-based medicine (CBM) in the treatment of pain due to rheumatoid arthritis (RA). Methods. We compared a CBM (Sativex) with placebo in a randomized, double-blind, parallel group study in 58 patients over 5 weeks of treatment. The CBM was administered by oromucosal spray in the evening and assessments were made the following morning. Efficacy outcomes assessed were pain on movement, pain at rest, morning stiffness and sleep quality measured by a numerical rating scale, the Short-Form McGill Pain Questionnaire (SF-MPQ) and the DAS28 measure of disease activity. Results. Seventy-five patients were screened and 58 met the eligibility criteria. Thirty-one were randomized to the CBM and 27 to placebo. Mean (S.D.) daily dose achieved in the final treatment week was 5.4 (0.84) actuations for the CBM and 5.3 (1.18) for placebo. In comparison with placebo, the CBM produced statistically significant improvements in pain on movement, pain at rest, quality of sleep, DAS28 and the SF-MPQ pain at present component. There was no effect on morning stiffness but baseline scores were low. The large majority of adverse effects were mild or moderate, and there were no adverse effect-related withdrawals or serious adverse effects in the active treatment group. Conclusions. In the first ever controlled trial of a CBM in RA, a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment. Whilst the differences are small and variable across the population, they represent benefits of clinical relevance and show the need for more detailed investigation in this indication.

The vast majority of substitute prescribing to opiate addicts in England and Wales is of oral methadone. The prescription of diamorphine, dipipanone and cocaine to addicts is allowed subject to the 1971 Misuse of Drugs Act. Prescription of these drugs has aroused international interest and controversy in the United Kingdom although research is scanty. This report is a description of the current attitudes about, and practice of, prescribing diamorphine, dipipanone and cocaine by medical practitioners in the addiction field in England and Wales. A questionnaire was devised and sent to drug services in England and Wales which provided a prescribing service. Among respondents who reported that they currently hold a licence for heroin, dipipanone or cocaine, the number of patients treated by each doctor varied widely; from a handful of patients to 100 heroin patients. Dosage currently used ranged from a minimum of 10 mg to a maximum of 1000 mg daily for heroin. Doses of dipipanone were lower. More respondents thought that heroin and dipipanone were clinically justified in some situations than thought that they should never be prescribed, while the opinions were reversed in the case of cocaine.

The effects of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg Delta-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 pm. The electroencephalogram was recorded during the sleep period (11 pm to 7 am). Performance, sleep latency, and subjective assessments of sleepiness and mood were measured from 8:30 am (10 hours after drug administration). There were no effects of 15 mg THC on nocturnal sleep. With the concomitant administration of the drugs (5 mg THC and 5 mg CBD to 15 mg THC and 15 mg CBD), there was a decrease in stage 3 sleep, and with the higher dose combination, wakefulness was increased. The next day, with 15 mg THC, memory was impaired, sleep latency was reduced, and the subjects reported increased sleepiness and changes in mood. With the lower dose combination, reaction time was faster on the digit recall task, and with the higher dose combination, subjects reported increased sleepiness and changes in mood. Fifteen milligrams THC would appear to be sedative, while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC.

Objectives: To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects. Design: A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods. Setting: Patients attended as outpatients, but took the CME at home. Subjects: Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1). Intervention: Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5–120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events. Results: Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME. Conclusions: Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.

1. The History of Cannabis As a Medicine: Ethan Russo 2. Growth and Morphology of Medicinal Cannabis: David Potter 3. The Breeding of Cannabis Cultivars for Pharmaceutical End-uses: Etienne De Meijer 5. Preclinical Pharmacology: Rik Musty 6. Receptors and Pharmacodynamics Natural and Synthtic Cannabinoids and Endocannabinoids: Roger Pertwee 7. Pharmacokinetics of Cannabinoids: Gabrielle Hawksworth : 8. Clinical Studies of Cannabis-based Medicine: Philip Robson, Geoffrey Guy 9. Cannabis in the Treatment of Neuropathic Pain: Willy Nottcutt 10. Forensic Control of Cannabis: Alex Allan 11. International Control of Cannabis Changing Attitudes: Alice Mead 4. The Evolution of Cannabis and Its Coevolution with the Human Cannabinoid Receptor: John Mcpartland 12. Developing a New Cannabis Based Medicine: Brian Whittle, Geoffrey Guy

Aim. To compare the characteristics of heroin, cocaine and amphetamine users having no history of contact with services with those of a group in contact. Method. Multiple agency sampling and field work which included ‘snowballing’ using ‘privileged access interviewers’. Each subject underwent a structured interview which included the Severity of Dependency Scale (SDS), and completed a confidential, self-report questionnaire. Setting. Three contrasting provincial urban locations. Participants. Five hundred and eighty-one regular users of the target drugs. Of these, 380 (65%) denied any contact with police or helping agencies in connection with drug use. Findings. Most zero-contact users (79%) expressed little or no concern about their drug use, and no wish for help or advice. They were much more likely to use stimulants only; less likely ever to inject any drug or, for those that did, to share equipment; less likely to use opioids, amphetamine or cocaine powder on a daily basis; more likely to use Ecstasy; and yielded significantly lower SDS scores for all target drugs save crack. Prevalence of crack use was lower, but the proportion of daily users was the same as in the contact group. Most (69%) contact users remained concerned about their drug use, but 58% expressed little or no confidence that local services could meet their needs. In both groups, SDS scores for cocaine powder were comparable to those for cannabis, LSD and Ecstasy. Of the 495 cannabis smokers identified (85% of the sample), 72% reported daily consumption. Conclusions. The findings are consistent with the hypothesis that ‘visible’ and ‘invisible’ drug users are distinct populations in terms of behavioural characteristics, vulnerability to compulsive use, and prevalence of drug-related problems or concern. Purchasers and providers with limited resources should concentrate on improving the range and quality of services for users already in contact rather than attempting to uncover invisible populations. On the basis of SDS scores, cocaine HCI seems to have a relatively modest addictive potential.

Since 1971 British doctors have been barred from prescribing cannabis under the Misuse of Drugs Act. Many otherwise law abiding people have subsequently thought it worthwhile to expose themselves to the risk, inconvenience, and expense of obtaining illegally a drug they believe can ease symptoms inadequately controlled by conventional medicines. Patients have told me how effective cannabis can be in relieving aches and pains, numbing the symptoms of opiate withdrawal, improving sleep, reducing anxiety, and alleviating the vomiting, anorexia, and depression associated with AIDS related disorders. Anecdotes such as these are all very well, but is there any scientific evidence that cannabis has real therapeutic value? The BMA has addressed this question with an excellent report, which begins by reviewing the pharmacology.1 Only a few of the 60 or so chemicals unique to Cannabis sativa (cannabinoids) have so far been studied, the best known of which is the main psychoactive ingredient, δ-9-tetrahydrocannabinol (THC). Specific cannabinoid receptors in the brain and in spleen macrophages, and naturally …

The purpose of this study was to assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD).A randomized, double-masked, placebo-controlled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of Delta-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects.Two hours after sublingual administration of 5 mg Delta-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP measurement. CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity were not significantly changed. One patient experienced a transient and mild paniclike reaction after Delta-9-THC administration.A single 5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated by most patients. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.

The literature relating to the acquisition, maintenance, and clinical significance of self-esteem reveals theoretical differences between earlier investigators. The nature of self-esteem remains controversial, and attention is drawn to some of the problems of construct validation and measurement. Despite the difficulties, self-esteem is a concept worthy of further pursuit. This will require a measuring instrument that captures the concept more effectively than those currently available.

SynopsisIn constructing a new self-report questionnaire for measuring self esteem, the aim has been to satisfy psychometric requirements without sacrificing the intuitive meaning of the concept. Self esteem is seen as a composite, and examination of its components may have more analytic or predictive value than ‘ global’ scores. Preliminary reliability and validity data are encouraging.

Summary In a cross-sectional study, the psychological profile of light social drinkers was compared with that of heavy social drinkers and alcohol-dependent patients who showed no evidence of clinical depression. The selection of psychological tests was based on the hypothesis that alcohol abuse and depression may sometimes be different expressions of the same disorder, and that the relationship between the two disorders may in pan be explicable in terms of shared psychological vulnerability factors. The tyests chosen were those thought most likely to predict vulnerability to depression. Dependent patients demonstrated significantly greater distortion of cognitive style than heavy social drinkers, who in turn rated significantly higher than light drinkers. Heavy social drinkers occupied a middle ground with regard to psychological profile between light drinkers and ‘alcoholics’, sharing some attributes with each. Possible implication for interventions by general practitioners are discussed.