Herbal Science Research - psychopharmacology

[Weighing the efficacy and safety of herbal medicine: the case of Kava-Kava]

Site Editor — Fri, 02 Nov 2007 06:25:03 -0700

[Weighing the efficacy and safety of herbal medicine: the case of Kava-Kava]: Harefuah. 2004 Aug;143(8):592-7, 621 Authors: Ben-Arye E, Reshef A, Berry E

Kava-Kava is an indigenous plant in the Pacific islands and has been traditionally used for centuries for both ceremonial and social purposes. The efficacy of the plant for treatment of anxiety states was recently acknowledged in randomized controlled trials. Although these trials support the safety of Kava for short term usage, a major concern was raised in accordance with emerging reports that relate Kava use to major hepatic damage, including a few cases of fulminant hepatitis that required liver transplantation or ended in death. As a result, most medical authorities in the West restricted or banned Kava use. This review discusses evidence of efficacy and safety in the use of Kava for treating patients with anxiety, as well as its meaning in the therapeutic context and patient-doctor dialogue.

PMID: 15523813 [PubMed - indexed for MEDLINE]

Herbal medicines in the treatment of psychiatric disorders: a systematic review.

Site Editor — Sun, 21 Oct 2007 05:48:23 -0700

Herbal medicines in the treatment of psychiatric disorders: a systematic review.: Phytother Res. 2007 Aug;21(8):703-16 Authors: Sarris J

This paper reports a critical review of 27 herbal medicines and formulas in treating a broad range of psychiatric disorders (in addition to anxiety and depression), including obsessive-compulsive, seasonal affective, bipolar depressive, psychotic, phobic and somatoform disorders. Ovid Medline, Pubmed and the Cochrane Library were searched for pharmacological and clinical evidence of herbal medicines with psychotropic activity. A forward search of later citations was also conducted. Whilst substantial high-quality evidence exists for the use of kava and St John's wort in the treatment of anxiety and depression respectively, currently there is insufficient robust clinical evidence for the use of many other herbal medicines in psychiatric disorders. Phytotherapies which potentially have significant use in psychiatry, and urgently require more research are Rhodiola rosea (roseroot) and Crocus sativus (saffron) for depression; Passiflora incarnata (passionflower), Scutellaria lateriflora (scullcap) and Zizyphus jujuba (sour date) for anxiety disorders; and Piper methysticum (kava) for phobic, panic and obsessive-compulsive disorders. While depression and anxiety are commonly researched, the efficacy of herbal medicines in other mental disorders requires attention. The review addresses current issues in herbal psychotherapy: herbal safety, future areas of application, the relationship of herbal medicine with pharmaceuticals and the potential prescriptive integration of phytomedicines with synthetic psychotropic medicines. Particular attention is given to clinical and safety issues with St John's wort and kava.

PMID: 17562566 [PubMed - indexed for MEDLINE]

Carpal tunnel syndrome, diabetic neuropathy, fibromyalgia, glucosamine and chondroitin, hypnosis [...], marijuana for pain.

Site Editor — Thu, 04 Oct 2007 05:30:00 -0700

Carpal tunnel syndrome, diabetic neuropathy, fibromyalgia, glucosamine and chondroitin, hypnosis in pain management, marijuana for pain.: J Pain Palliat Care Pharmacother. 2007;21(2):61-7 Authors: Fishman SM

This feature presents information for patients in a question and answer format. It is written to simulate actual questions that many pain patients ask and to provide answers in a context and language that most pain patients will comprehend. Issues addressed in this issue are carpel tunnel syndrome, fibromyalgia, glucosamine and chondroitin, hypnosis, marijuana.

PMID: 17844729 [PubMed - indexed for MEDLINE]

The toxicology of cannabis and cannabis prohibition.

Site Editor — Sun, 30 Sep 2007 02:38:23 -0700

The toxicology of cannabis and cannabis prohibition.: Chem Biodivers. 2007 Aug;4(8):1744-69 Authors: Grotenhermen F

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.

PMID: 17712818 [PubMed - indexed for MEDLINE]

Medicinal chemistry endeavors around the phytocannabinoids.

Site Editor — Sun, 30 Sep 2007 02:37:45 -0700

Medicinal chemistry endeavors around the phytocannabinoids.: Chem Biodivers. 2007 Aug;4(8):1707-28 Authors: Stern E, Lambert DM

Over the past 50 years, a considerable research in medicinal chemistry has been carried out around the natural constituents of Cannabis sativa L. Following the identification of Delta9-tetrahydrocannabinol (Delta9-THC) in 1964, critical chemical modifications, e.g., variation of the side chain at C3 and the opening of the tricyclic scaffold, have led to the characterization of potent and cannabinoid receptor subtype-selective ligands. Those ligands that demonstrate high affinity for the cannabinoid receptors and good biological efficacy are still used as powerful pharmacological tools. This review summarizes past as well as recent developments in the structure-activity relationships of phytocannabinoids.

PMID: 17712816 [PubMed - indexed for MEDLINE]

Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.

Site Editor — Sun, 30 Sep 2007 02:37:02 -0700

Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.: Chem Biodivers. 2007 Aug;4(8):1729-43 Authors: Russo EB, Guy GW, Robson PJ

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.

PMID: 17712817 [PubMed - indexed for MEDLINE]

The Future of Cannabinoids as Analgesic Agents: A Pharmacologic, Pharmacokinetic, and Pharmacodynamic Overview.

Site Editor — Wed, 26 Sep 2007 19:12:49 -0700

The Future of Cannabinoids as Analgesic Agents: A Pharmacologic, Pharmacokinetic, and Pharmacodynamic Overview.: Am J Ther. 2007 September/October;14(5):475-483 Authors: McCarberg BH, Barkin RL

For thousands of years, physicians and their patients employed cannabis as a therapeutic agent. Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed. However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored. Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies. Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions. Nevertheless, despite promising preclinical and early clinical data, particularly in the areas of inflammation and nociception, development challenges abound. Tetrahydrocannabinol (THC) and other CB1 receptor agonists can have an undesirable CNS impact, and, in many cases, dose optimization may not be realizable before onset of excessive side effects. In addition, complex botanically derived cannabinoid products must satisfy the demanding criteria of the U.S. Food and Drug Association's approval process. Recent agency guidance suggests that these obstacles are not insurmountable, although cannabis herbal material ("medical marijuana") may present fatal uncertainties of quality control and dosage standardization. Therefore, formulation, composition, and delivery system issues will affect the extent to which a particular cannabinoid product may have a desirable risk-benefit profile and acceptable abuse liability potential. Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders. Further research is warranted to explore the therapeutic potential of this area.

PMID: 17890938 [PubMed - as supplied by publisher]

[...] Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.

Site Editor — Sat, 23 Jun 2007 05:37:43 -0700

The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.:

The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.

Menopause. 2007 Mar-Apr;14(2):270-83

Authors: Kaszkin-Bettag M, Ventskovskiy BM, Kravchenko A, Rettenberger R, Richardson A, Heger PW, Heger M

OBJECTIVE: To investigate the efficacy of the special extract ERr 731 from the roots of Rheum rhaponticum compared with placebo on anxiety, health state, and general well-being in perimenopausal women. DESIGN: This study is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial, in which 109 perimenopausal women with climacteric complaints and anxiety received either 1 enteric coated tablet of ERr 731 (n=54) or placebo (n=55) daily for 12 weeks. The Hamilton Anxiety Scale, the Menopause Rating Scale II, the Women's Health Questionnaire, and the Psychological General Well-Being Index were used to measure anxiety, health state, and subjective psychological well-being. RESULTS: The results demonstrate that ERr 731 is highly effective in reducing anxiety in perimenopausal women compared with placebo. After 12 weeks, the Hamilton Anxiety Scale total score decreased significantly with ERr 731 (from 27.5+/-6.8 to 9.4+/-4.2 points) compared with placebo (from 25.1+/-6.0 to 21.6+/-8.6 points). ERr 731 also reduced the Hamilton Anxiety Scale factor scores for somatic and psychic anxiety. After 12 weeks, a reduction in the severity of anxiety from "moderate" or "severe" to "slight" was observed in 33 of 39 ERr 731 women completing the double-blind phase, which correlated well with the reduction in number and severity of hot flushes. This was reflected by a high rate of ERr 731 women reporting a marked improvement in health state and general well-being. CONCLUSIONS: ERr 731 is an effective medication for women with menopause-related anxiety and improves their health state and general well-being.

PMID: 17213754 [PubMed - indexed for MEDLINE]

Predictors of betel quid chewing behavior and cessation patterns in Taiwan aborigines.

Site Editor — Wed, 30 May 2007 01:26:20 -0700

Predictors of betel quid chewing behavior and cessation patterns in Taiwan aborigines.: BMC Public Health. 2006;6:271 Authors: Lin CF, Wang JD, Chen PH, Chang SJ, Yang YH, Ko YC

BACKGROUND: Betel quid, chewed by about 600 million people worldwide, is one of the most widely used addictive substances. Cessation factors in betel quid chewers are unknown. The present study explores prevalence and the quit rate of betel quid chewing in Taiwan aborigines. Our goal was to delineate potential predictors of chewing cessation. METHODS: A stratified random community-based survey was designed for the entire aborigines communities in Taiwan. A total of 7144 participants were included between June 2003 and May 2004 in this study. Information on sociodemographic characteristics, such as gender, age, obesity, education years, marital status, ethnicity, and habits of betel quid chewing, smoking and drinking was collected by trained interviewers. RESULTS: The prevalence of betel quid chewers was 46.1%. Betel quid chewing was closely associated with obesity (OR = 1.61; 95% CI: 1.40-1.85). Betel quid chewers were most likely to use alcohol and cigarettes together. Quit rate of betel quid chewers was 7.6%. Betel quid chewers who did not drink alcohol were more likely to quit (OR = 1.89; 95% CI: 1.43-2.50). Alcohol use is a significant factor related to cessation of betel quid chewing, but smoking is not. CONCLUSION: Taiwan aborigines have a high prevalence of betel quid chewers and a low quit rate. Alcohol use is strongly association with betel quid chewing. Efforts to reduce habitual alcohol consumption might be of benefit in cessation of betel quid chewing.

Dietary phytoestrogen intake and cognitive function in older women.

Site Editor — Wed, 30 May 2007 01:05:28 -0700

Dietary phytoestrogen intake and cognitive function in older women.: J Gerontol A Biol Sci Med Sci. 2007 May;62(5):556-62 Authors: Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, van der Schouw YT

BACKGROUND: Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. METHODS: We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. RESULTS: No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). CONCLUSIONS: This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

Update and critique of natural remedies as antidepressant treatments.

Site Editor — Wed, 30 May 2007 00:59:46 -0700

Update and critique of natural remedies as antidepressant treatments.: Psychiatr Clin North Am. 2007 Mar;30(1):51-68 Authors: Mischoulon D

Natural medications such as St. John's Wort, SAMe, and omega-3 fatty acids eventually may prove to be valuable additions to the psychiatrist's pharmacologic armamentarium, both as monotherapy and as adjunctive therapy for mood disorders. Current research data are compelling, from a standpoint of both efficacy and safety, but before clinicians can recommend these as first-line treatments, more well-designed controlled studies in large patient populations are needed. During the past decade, the National Institutes of Health, the National Institute for Mental Health, and the National Center for Complementary and Alternative Medicine have widened their support for research on the efficacy and safety of alternative treatments, and increasing numbers of academic institutions are undertaking large-scale, multicenter studies on the natural medications reviewed here, as well as others. These studies should help answer some of the yet-unsettled questions about natural medications. Psychiatrists who are considering recommending natural antidepressants to their patients should emphasize that these treatments are relatively unproven and that it remains to be seen whether they would be appropriate or preferable to the conventional psychotropic agents. in the absence of more conclusive data, the best candidates for alternative treatments may be patients for whom a delay in adequate treatment would not be devastating(eg, the mildly symptomatic patient who has a strong interest in natural remedies). Other good candidates may include patients who have been unresponsive to conventional antidepressants or particularly intolerant of side effects; these patients, however, often are the most difficult to treat, and alternative agents seem best suited for the mildly ill. Care should be taken with patients who are taking multiple medications, in view of adverse drug-drug interactions that have emerged with increased use of alternative treatments. Finally, as with all psychotropic agents, natural medications should be used preferably under the supervision of a physician.

Salvinorin A: from natural product to human therapeutics.

Site Editor — Wed, 30 May 2007 00:57:46 -0700

Salvinorin A: from natural product to human therapeutics.: Mol Interv. 2006 Oct;6(5):257-65 Authors: Vortherms TA, Roth BL

The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been used for divination and shamanism by the Mazatecs. Over the past decade or so, S. divinorum has been increasingly used recreationally. The neoclerodane diterpene salvinorin A is the active component of S. divinorum, and recently, the kappa opioid receptor (KOR) has been identified, in vitro and in vivo, as its molecular target. The discovery of KOR as the molecular target of salvinorin A has opened up many opportunities for drug discovery and drug development for a number of psychiatric and non-psychiatric disorders.

Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.

Site Editor — Fri, 11 May 2007 15:54:21 -0700

Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.: Eur J Neurol. 2007 Mar;14(3):290-6 Authors: Collin C, Davies P, Mutiboko IK, Ratcliffe S,

Symptoms relating to spasticity are common in multiple sclerosis (MS) and can be difficult to treat. We have investigated the efficacy, safety and tolerability of a standardized oromucosal whole plant cannabis-based medicine (CBM) containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), upon spasticity in MS. A total of 189 subjects with definite MS and spasticity were randomized to receive daily doses of active preparation (n = 124) or placebo (n = 65) in a double blind study over 6 weeks. The primary endpoint was the change in a daily subject-recorded Numerical Rating Scale of spasticity. Secondary endpoints included a measure of spasticity (Ashworth Score) and a subjective measure of spasm. The primary efficacy analysis on the intention to treat (ITT) population (n = 184) showed the active preparation to be significantly superior (P = 0.048). Secondary efficacy measures were all in favour of active preparation but did not achieve statistical significance. The responder analysis favoured active preparation, 40% of subjects achieved >30% benefit (P = 0.014). Eight withdrawals were attributed to adverse events (AEs); six were on active preparation and two on placebo. We conclude that this CBM may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS.

A case series of patients using medicinal marihuana for management of chronic pain...

Site Editor — Wed, 31 Jan 2007 19:16:02 -0800

A case series of patients using medicinal marihuana for management of chronic pain under the Canadian Marihuana Medical Access Regulations.: J Pain Symptom Manage. 2006 Nov;32(5):497-501 Authors: Lynch ME, Young J, Clark AJ

The Canadian Marihuana Medical Access Regulations (MMAR) program allows Health Canada to grant access to marihuana for medical use to those who are suffering from grave and debilitating illnesses. This is a report on a case series of 30 patients followed at a tertiary care pain management center in Nova Scotia who have used medicinal marihuana for 1-5 years under the MMAR program. Patients completed a follow-up questionnaire containing demographic and dosing information, a series of 11-point numerical symptom relief rating scales, a side effect checklist, and a subjective measure of improvement in function. Doses of marihuana ranged from less than 1 to 5g per day via the smoked or oral route of administration. Ninety-three percent of patients reported moderate or greater pain relief. Side effects were reported by 76% of patients, the most common of which were increased appetite and a sense of well-being, weight gain, and slowed thoughts. Limitations of the study include self-selection bias, small size, and lack of a control group. The need for further study using controlled trials is discussed along with an overview of the MMAR program.

Valerian for anxiety disorders.

Site Editor — Sat, 20 Jan 2007 16:27:08 -0800

Valerian for anxiety disorders.: Cochrane Database Syst Rev. 2006;(4):CD004515 Authors: Miyasaka LS, Atallah AN, Soares BG

BACKGROUND: Anxiety disorders are very common mental health problems in the general population and in primary care settings. Herbal medicines are popular and used worldwide and might be considered as a treatment option for anxiety if shown to be effective and safe. OBJECTIVES: To investigate the effectiveness and safety of valerian for treating anxiety disorders. SEARCH STRATEGY: Electronic searches: The Cochrane Collaboration Depression, Anxiety and Neurosis Cochrane Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) searched on 04/08/2006, MEDLINE, Lilacs. References of all identified studies were inspected for additional studies. First authors of each included study, manufacturers of valerian products, and experts in the field were contacted for information regarding unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials of valerian extract of any dose, regime, or method of administration, for people with any primary diagnosis of general anxiety disorder, anxiety neurosis, chronic anxiety status, or any other disorder in which anxiety is the primary symptom (panic disorder, obsessive compulsive disorder, social phobia, agoraphobia, other types of phobia, postraumatic stress disorder). Effectiveness was measured using clinical outcome measures and other scales for anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, extracted and entered data, and performed the trial quality assessments. Where disagreements occurred, the third review author was consulted. Methodological quality of included trials was assessed using Cochrane Handbook criteria. For dichotomous outcomes, relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) was calculated, with their respective 95% confidence intervals. MAIN RESULTS: One RCT involving 36 patients wih generalised anxiety disorder was eligible for inclusion. This was a 4 week pilot study of valerian, diazepam and placebo. There were no significant differences between the valerian and placebo groups in HAM-A total scores, or in somatic and psychic factor scores. Similarly, there were no significant differences in HAM-A scores between the valerian and diazepam groups, although based on STAI-Trait scores, significantly greater symptom improvement was indicated in the diazepam group. There were no significant differences between the three groups in the number of patients reporting side effects or in dropout rates. AUTHORS' CONCLUSIONS: Since only one small study is currently available, there is insufficient evidence to draw any conclusions about the efficacy or safety of valerian compared with placebo or diazepam for anxiety disorders. RCTs involving larger samples and comparing valerian with placebo or other interventions used to treat of anxiety disorders, such as antidepressants, are needed.

The psychopharmacology of European herbs with cognition-enhancing properties.

Site Editor — Sat, 20 Jan 2007 00:25:31 -0800

The psychopharmacology of European herbs with cognition-enhancing properties.: Curr Pharm Des. 2006; 12(35): 4613-23 Authors: Kennedy DO, Scholey AB

Extensive research suggests that a number of plant-derived chemicals and traditional Oriental herbal remedies possess cognition-enhancing properties. Widely used current treatments for dementia include extracts of Ginkgo biloba and several alkaloidal, and therefore toxic, plant-derived cholinergic agents. Several non-toxic, European herbal species have pan-cultural traditions as treatments for cognitive deficits, including those associated with ageing. To date they have not received research interest commensurate with their potential utility. Particularly promising candidate species include sage (Salvia lavandulaefolia/officinalis), Lemon balm (Melissa officinalis) and rosemary (Rosmarinus officinalis). In the case of sage, extracts possess anti-oxidant, estrogenic, and anti-inflammatory properties, and specifically inhibit butyryl- and acetyl-cholinesterase. Acute administration has also been found to reliably improve mnemonic performance in healthy young and elderly cohorts, whilst a chronic regime has been shown to attenuate cognitive declines in sufferers from Alzheimer's disease. In the case of Melissa officinalis, extracts have, most notably, been shown to bind directly to both nicotinic and muscarinic receptors in human brain tissue. This property has been shown to vary with extraction method and strain. Robust anxiolytic effects have also been demonstrated following acute administration to healthy humans, with mnemonic enhancement restricted to an extract with high cholinergic binding properties. Chronic regimes of aromatherapy and essential oil respectively have also been shown to reduce agitation and attenuate cognitive declines in sufferers from dementia. Given the side effect profile of prescribed cholinesterase inhibitors, and a current lack of a well tolerated nicotinic receptor agonist, these herbal treatments may well provide effective and well-tolerated treatments for dementia, either alone, in combination, or as an adjunct to conventional treatments.

Ergot and its alkaloids.

Site Editor — Thu, 04 Jan 2007 18:11:45 -0800

Ergot and its alkaloids.: Am J Pharm Educ. 2006 Oct 15;70(5):98 Authors: Schiff PL

This manuscript reviews the history and pharmacognosy of ergot, and describes the isolation/preparation, chemistry, pharmacodynamics, and pharmacotherapeutics of the major ergot alkaloids and their derivatives. A brief discussion of the hallucinogenic properties of lysergic acid diethylamide is also featured. An abbreviated form of the material found in this paper is presented in a 4-hour didactic format to third-professional year PharmD students as part of their study of vascular migraine headaches, Parkinson's disease, and naturally occurring hallucinogens/hallucinogen derivatives in the modular course offering Neurology/Psychiatry.

[Salvia divinorum--representation of a new drug in the Internet]

Site Editor — Wed, 04 Oct 2006 18:53:01 -0700

[Salvia divinorum--representation of a new drug in the Internet]: Gesundheitswesen. 2006 May; 68(5): 323-7 Siemann H, Specka M, Schifano F, Deluca P, Scherbaum N

AIM OF THE STUDY: The German pages of the Internet were searched for the presence of the hallucinogenic herbal drug Salvia divinorum, which is not dealt with in current addiction medicine or psychiatric text books. The investigation is part of the EU sponsored project "Psychonaut" as preparatory work for the development of an Internet-based early warning system. METHODS: The first 100 websites of the search using "Salvia divinorum" were compared with the search results for "cannabis" and "LSD". The following aspects of the sites were especially analyzed: the originator, marketing of drugs, and the attitude towards drug use. RESULTS: Salvia was offered for sale on approximately a third of the sites (29%); cannabis and LSD were not marketed on any sites. Official websites such as those from governmental organizations or universities were seldom found when searching for "Salvia divinorum", and then only under the last hits. The percentage of institutional sites (e. g. public organizations) were 12% with Salvia, 21% with cannabis, and 38% with LSD. A drug-friendly attitude was found at 64 % of the sites with regard to Salvia, 58% for cannabis, and 24% for LSD. CONCLUSION: The drug help system must be aware of that the Internet is a source of drug-related information, and of drug trade. As this investigation shows, sites often have a drug-friendly attitude. The low availability of official information on Salvia divinorum (also outside the Internet) relative to the presence of drug-friendly or drug trading sites is an indication that new trends of drug consumption can be tracked in the Internet before they will be found in official literature.

Medical use of cannabis in the Netherlands.

Site Editor — Fri, 09 Jun 2006 07:21:58 -0700

Medical use of cannabis in the Netherlands.: Neurology. 2005 Mar 8;64(5):917-9 Authors: Gorter RW, Butorac M, Cobian EP, van der Sluis W

The authors investigated the indications for cannabis prescription in the Netherlands and assessed its efficacy and side effects. A majority (64.1%) of patients reported a good or excellent effect on their symptoms. Of these patients, approximately 44% used cannabis for >/=5 months. Indications were neurologic disorders, pain, musculoskeletal disorders, and cancer anorexia/cachexia. Inhaled cannabis was perceived as more effective than oral administration. Reported side effects were generally mild.

Isolation and characterization of yuremamine, a new phytoindole.

Site Editor — Fri, 09 Jun 2006 07:15:47 -0700

Isolation and characterization of yuremamine, a new phytoindole.: Planta Med. 2005 Nov;71(11):1053-7 Authors: Vepsäläinen JJ, Auriola S, Tukiainen M, Ropponen N, Callaway JC

Yuremamine was isolated and characterized from the stem bark of Mimosa tenuiflora. This plant is still used by indigenous peoples in North-eastern Brazil to make yurema, a psychoactive beverage that is used for medico-religious purpose ( jurema preta or vinho da jurema, in Portuguese). The characterization of this novel compound by NMR and mass spectrometry introduces a new class of phytoindoles.

Multiple aspects of hair analysis for opiates: methodology, clinical and workplace populations...

Site Editor — Fri, 09 Jun 2006 07:15:23 -0700

Multiple aspects of hair analysis for opiates: methodology, clinical and workplace populations, codeine, and poppy seed ingestion.: J Anal Toxicol. 2005 Oct;29(7):696-703

Authors: Hill V, Cairns T, Cheng CC, Schaffer M

Levels of morphine, 6-monoacetylmorphine (MAM) and codeine in hair in both clinical and workplace subjects are presented. Aggressive wash procedures, consisting of 1 isopropanol wash, three 30-min, and two 1-h buffer washes, followed by digestion, extraction and confirmation of digested samples, resulted in values from the cutoff of 2 ng morphine/10 mg hair to greater than 200 ng/10 mg hair. Both morphine and MAM were present above the cutoff in all hair samples from 69 clinical subjects. Only 39 of the 69 heroin-using subjects had urine tests positive for 6-MAM. In a study of morphine in hair following poppy seed consumption, ten subjects ingested 150 g of poppy seed over 3 weeks. Urine samples were collected on the days of poppy seed ingestion and hair samples were taken in the 5th week of the study. The range among the 10 subjects of the highest urine value for each subject was 2929 to 13,827 ng morphine/mL. Hair morphine levels were 0.05-0.48 ng/10 mg hair (average 0.17 ng/10 mg hair). Hair opiate levels of workplace subjects ranged somewhat lower than those of clinical subjects. While all clinical hair samples contained MAM, many workplace samples did not. From workplace samples, a maximum amount of morphine likely to be present from codeine use was 0-3.7% of the codeine in the hair.

Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma...

Site Editor — Fri, 09 Jun 2006 04:32:34 -0700

Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract.: J Anal Toxicol. 2005 Nov-Dec;29(8):782-9 Authors: Nadulski T, Sporkert F, Schnelle M, Stadelmann AM, Roser P, Schefter T, Pragst F

Besides the psychoactive Delta(9)-tetrahydrocannabinol (THC), hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol (CBD) and of the degradation product cannabinol (CBN). The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. Therefore, a method for the simultaneous quantitative determination of THC, its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), CBD and CBN from plasma was developed. The method was based on automatic solid-phase extraction with C(18) ec columns, derivatization with N,O-bistrimethylsilyltrifluoroacetamide (BSTFA), and gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) with deuterated standards. The limits of detection were between 0.15 and 0.29 ng/mL for THC, 11-OH-THC, THC-COOH, and CBD and 1.1 ng/mL for CBN. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract. The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL (mean 4.05 ng/mL) for THC, 1.8 and 12.3 ng/mL (mean 4.9 ng/mL) for 11-OH-THC, 19 and 71 ng/mL (mean 35 ng/mL) for THC-COOH, and 0.2 and 2.6 ng/mL (mean 0.95 ng/mg) for CBD. The peak concentrations (mean values) of THC, 11-OH-THC, THC-COOH, and CBD were observed at 56, 82, 115, and 60 min, respectively, after intake. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. Therefore, the concentration ratio 11-OH-THC/THC was discussed as a criterion for distinguishing oral from inhalative cannabis consumption.

[The situation of patients with dementia may be rectified by Ginkgo biloba. Results of a health services research study...

Site Editor — Fri, 09 Jun 2006 03:52:17 -0700

[The situation of patients with dementia may be rectified by Ginkgo biloba. Results of a health services research study concerning the ability of patients with dementia, quality of life of the nursing family members and total treatment costs]: MMW Fortschr Med. 2005 Oct 6;147 Suppl 3:127-33 Authors: Heinen-Kammerer T, Motzkat K, Daniel D, Gertz HJ, Koller M, Lorenz W, Pilartz H, Zimmer B, Habs M, von den Driesch V, Rychlik R

BACKGROUND AND ISSSUES: Ginkgo biloba-extracts are often used in therapy of patients with dementia. In this study, benefit and structure of Ginkgo biloba-extract EGb 761 in treatment of patients with dementia was examined. PATIENTS AND METHODS: For the assessment of quality of life of care-taking relatives and patients as well as treatment costs were documented. The study was conducted as a non-randomised, two-armed cohort study with an open design for 683 slightly or moderately demented patients, aged between 65 and 80 years. Society's perspective was taken. Barthel-Index and MMST were also documented. Because of significant differences at inclusion of both cohorts, a matched-pairs-analysis and multiple regression analysis conducted. RESULTS: According to PLC a significant improvement in quality-of-life of care-taking relatives (p < 0.001) and patients (positive mood p = 0.018, negative mood p < 0.001) was only observed in the Ginkgo-cohort. Also Barthel-Index indicated an improvement in the Ginkgo-cohort (p < or = 0,001). MMST-scores increased significantly only in the Ginkgo-cohort (p < 0.001). Average total cost per patient amounted to 3.614,75 euro in the standard-cohort, whereas these costs per patient in the Ginkgo-cohort amounted to 3.031,78 euro (p = 0.067). Results were confirmed by matched-pairs-analysis. RESULTS: Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attributes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.

Drug abuse in Slovak Republic.

Site Editor — Fri, 09 Jun 2006 03:49:20 -0700

Drug abuse in Slovak Republic.: Przegl Lek. 2005;62(6):357-60 Authors: Kresanek J, Plackova S, Caganova B, Klobusicka Z

The drug abusing structure has dramatically changed since 1989. While in 1989 the sniffing of the fluid drugs represented 98% of the global drug abuse, the most abused drugs were: heroin, marijuana, cocaine, amphetamine and its derivatives. During last 10 years situation with drug abuse has changed. Currently the most abused drugs: cannabinoides, amphetamines. The plant drugs (Datura stramonium, hallucinogenic mushrooms Psilocybe semilanceata, nutmeg--the seed of Myristica fragrans) combined with the alcohol are popular among the young abusers. According to an analysis of the phone consultations in our Toxicological Information Centre (TIC) we found out, that the number of intoxications with the plant drugs has increased five times during the last year (comparing with the year 2000), because of their easy availability, low price and quick spreading of information.

Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.

Site Editor — Fri, 09 Jun 2006 03:32:55 -0700

Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.: J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1664-9 Authors: Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ

OBJECTIVE: To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study. METHODS: In total, 630 patients with stable MS with muscle spasticity from 33 UK centres were randomised to receive oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabis extract, or placebo in the main 15 week CAMS study. The primary outcome was change in the Ashworth spasticity scale. Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK Neurological Disability Score, postal Barthel Index, General Health Questionnaire-30, and a series of nine category rating scales. Following the main study, patients were invited to continue medication, double blinded, for up to 12 months in the follow up study reported here. RESULTS: Intention to treat analysis of data from the 80% of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months (Delta(9)-THC mean reduction 1.82 (n = 154, 95% confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n = 172, 95% CI -0.99 to 1.19), placebo -0.23 (n = 176, 95% CI -1.41 to 0.94); p = 0.04 unadjusted for ambulatory status and centre, p = 0.01 adjusted). There was suggestive evidence for treatment effects of Delta(9)-THC on some aspects of disability. There were no major safety concerns. Overall, patients felt that these drugs were helpful in treating their disease. CONCLUSIONS: These data provide limited evidence for a longer term treatment effect of cannabinoids. A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS.

Sativex for the management of multiple sclerosis symptoms.

Site Editor — Fri, 09 Jun 2006 03:32:45 -0700

Sativex for the management of multiple sclerosis symptoms.: Issues Emerg Health Technol. 2005 Sep;(72):1-4 Authors: Perras C

Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.

Hallucinogenic botanicals of America: A growing need for focused drug education and research.

Site Editor — Fri, 09 Jun 2006 03:26:40 -0700

Hallucinogenic botanicals of America: A growing need for focused drug education and research: Halpern JH, Sewell RA. Biological Psychiatry Laboratory, Alcohol and Drug Abuse Research Center, Harvard Medical School.

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.

Cannabis and tobacco smoke are not equally carcinogenic

Site Editor — Fri, 09 Jun 2006 03:24:10 -0700

Cannabis and tobacco smoke are not equally carcinogenic:

More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.

Determination of salvinorins and divinatorins in Salvia divinorum leaves by liquid chromatography/multistage mass spectrometry.

Site Editor — Fri, 09 Jun 2006 03:21:16 -0700

Determination of salvinorins and divinatorins in Salvia divinorum leaves by liquid chromatography/multistage mass spectrometry.: Rapid Commun Mass Spectrom. 2005 Dec 6;20(2):131-136 Authors: Medana C, Massolino C, Pazzi M, Baiocchi C

Salvinorin A is the most potent naturally occurring hallucinogen known and rivals synthetic LSD in potency. Structurally it belongs to the neoclerodane diterpenoids, and it is the only known non-nitrogenous kappa-opioid-selective agonist. Salvia divinorum (Diviner's sage) is a member of the mint family that was used in ancient Mexican traditional practices. Today it is widely cultivated in Europe as a recreational marijuana substitute; it is illegal to buy, sell or possess the plant or the active principle in some countries. Six different salvinorins and three divinatorins have been isolated from Salvia divinorum leaves. The ion fragmentation, separation and quantitation of these diterpenes by liquid chromatography/electrospray ionization multistage mass spectrometry (LC/ESI-MS(n)) are described. The importance of LC in herbal extract determination and the chemical diagnostic power of MS(n) in the analysis of classes of natural organic products are discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.