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Posted 27 October 2017 - 08:50 AM
This is interesting Vapor8. I will do some digging into this when I get a chance and see what I can find. I am sure the history of this mushroom as an illegal street hallucinogen will hold back any consideration of its use. As they say....more to follow.
Posted 27 October 2017 - 11:48 AM
psilocybin micro-dose treatment
Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of mushrooms.As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks. In 1959, the Swiss chemist Albert Hofmann isolated the active principle psilocybin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic psychotherapy. Although the increasingly restrictive drug laws of the late 1960s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms.
Once ingested, psilocybin is rapidly metabolized to psilocin, which then acts on serotonin receptors in the brain. The mind-altering effects of psilocybin typically last from two to six hours, although to individuals under the influence of psilocybin, the effects may seem to last much longer, since the drug can distort the perception of time. Since the 1990s, there has been a renewal of scientific research into the potential medical and psychological therapeutic benefits of psilocybin for treating conditions including obsessive-compulsive disorder(OCD), Post traumatic stress disorder, social anxiety, treatment-resistant depression, cluster heqadaches, and anxiety related to terminal cancer.
Most of the comparatively few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. Probably the most common cause of hospital admissions resulting from psychedelic mushroom usage involve "bad trips" or panic reactions, in which affected individuals become extremely anxious, confused, agitated, or disoriented. Accidents, self-injury, or suicide attempts can result from serious cases of acute psychotic episodes.
Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violent behavior, suicidal thoughts,schizophrenia-like psychosis,and convulsions have been reported in the literature. A 2005 survey conducted in the United Kingdom found that almost a quarter of those who had used psilocybin mushrooms in the past year had experienced a panic attack. Other adverse effects less frequently reported include paranoia, confusion, prolonged derealization (disconnection from reality), and mania. Psilocybin usage can temporarily induce a state of depersonalization disorder. Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization.
Recent evidence, however, has suggested against the contention that the use of psilocybin puts one at risk for developing long lasting mental disorders. An analysis of information from the National Survey on Drug Use and Health showed that the use of psychedelic drugs such as psilocybin is associated with significantly reduced odds of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt.
Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once a week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect
\l "The federal law that specifically banned psilocybin and psilocin was enacted on October 24, 1968. The substances were said to have "a high potential for abuse", "no currently accepted medical use," and "a lack of accepted safety". On October 27, 1970, both psilocybin and psilocin became classified as Schedule I drugs and were simultaneously labeled "hallucinogens" under a section of the Comprehensive Drug Abuse Prevention and Control Act known as the Controlled Substances Act. Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit.
Biol Psychiatry. 2015 Oct 15;78(8):572-81. doi: 10.1016/j.biopsych.2014.04.010. Epub 2014 Apr 26.
Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.
Kraehenmann R1, Preller KH2, Scheidegger M3, Pokorny T2, Bosch OG4, Seifritz E4, Vollenweider FX2.
The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change.
This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart.
Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state.
These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.
J Psychopharmacol. 2015 Nov;29(11):1182-90. doi: 10.1177/0269881115609019. Epub 2015 Oct 6.
Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin.
J Psychoactive Drugs. 2014 Nov-Dec;46(5):393-5. doi: 10.1080/02791072.2014.963754.
Psilocybin and Obsessive Compulsive Disorder.
Obsessive Compulsive Disorder (OCD) is a psychiatric disorder with considerable morbidity and mortality. This condition disables many individuals and is often refractory to treatment. Research suggests that serotonin plays a role in OCD symptom reduction. We present a case of an individual who successfully used psilocybin, a serotonergic agent, to reduce the core symptoms of OCD for several years. Although not endorsing this form of treatment, we feel that the successful use of this agent highlights the role of serotonergic factors in OCD and the need for further, legitimate research into the value of psilocybin in the treatment of anxiety disorders.
Arch Gen Psychiatry. 2011 Jan;68(1):71-8. doi: 10.1001/archgenpsychiatry.2010.116. Epub 2010 Sep 6.
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.
Psychopharmacology (Berl). Author manuscript; available in PMC 2012 Dec 1.
Published in final edited form as:
Psychopharmacology (Berl). 2011 Dec; 218(4): 649–665. Published online 2011 Jun 15. doi: 10.1007/s00213-011-2358-5
Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects
Drug Alcohol Depend. 2012 Jun 1;123(1-3):132-40. doi: 10.1016/j.drugalcdep.2011.10.029. Epub 2011 Nov 29.
Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.
PLoS One. 2012;7(2):e30800. doi: 10.1371/journal.pone.0030800. Epub 2012 Feb 17.
Prediction of psilocybin response in healthy volunteers.
Studerus E1, Gamma A, Kometer M, Vollenweider FX.
Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.
Neurology. 2006 Jun 27;66(12):1920-2.
Response of cluster headache to psilocybin and LSD.
J Psychopharmacol. 2011 Nov;25(11):1434-52. doi: 10.1177/0269881110382466. Epub 2010 Sep 20.
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.
Studerus E1, Kometer M, Hasler F, Vollenweider FX.
Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.
Asian J Psychiatr. 2016 Dec;24:51-52. doi: 10.1016/j.ajp.2016.08.010. Epub 2016 Aug 23.
Return of the psychedelics: Psilocybin for treatment resistant depression.
Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested.
Neuroreport. 1998 Dec 1;9(17):3897-902.
Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.
Chudoku Kenkyu. 2016 Mar;29(1):33-5.
[Three cases of acute serotonin syndrome due to psilocybin mushroom poisoning].
J Psychopharmacol. 2007 Jan;21(1):50-64. Epub 2006 May 19.
Effects of psilocybin on time perception and temporal control of behaviour in humans.
Wittmann M1, Carter O, Hasler F, Cahn BR, Grimberg U, Spring P, Hell D, Flohr H, Vollenweider FX.
Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.
Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.
Carhart-Harris RL1, Bolstridge M2, Rucker J3, Day CM2, Erritzoe D2, Kaelen M2, Bloomfield M4, Rickard JA5, Forbes B6, Feilding A7, Taylor D8, Pilling S9, Curran VH10, Nutt DJ2.
Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.
In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.
Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.
This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.
Ther Adv Psychopharmacol. 2017 Jan;7(1):54-56. doi: 10.1177/2045125316676092. Epub 2016 Oct 27.
Role of psilocybin in the treatment of depression.
Mahapatra A1, Gupta R2.
Psilocybin is a naturally occurring alkaloid, pharmacologically similar to the classic hallucinogen lysergic acid diethylamide (LSD). Although primarily used as a recreational drug or an entheogen in particular cultural settings, recent population based studies have shown that it does not lead to serious physical or mental health problems or dependent use. In view of recent work demonstrating psilocybin's potential to increase subjective sense of wellbeing and because of its novel mechanism of 5-HT2A serotonin receptor agonism, it is being explored for possible therapeutic utility in mood and anxiety disorders.
Neurotherapeutics. 2017 Jul;14(3):734-740. doi: 10.1007/s13311-017-0542-y.
Potential Therapeutic Effects of Psilocybin.
Johnson MW1, Griffiths RR2,3.
Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.
Sci Rep. 2017 Oct 13;7(1):13187. doi: 10.1038/s41598-017-13282-7.
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.
Carhart-Harris RL1, Roseman L2,3, Bolstridge M2, Demetriou L4,5, Pannekoek JN2,6, Wall MB2,7,4, Tanner M4, Kaelen M2, McGonigle J4, Murphy K8, Leech R3, Curran HV7, Nutt DJ2.
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.
Clin Pharmacokinet. 2017 Mar 28. doi: 10.1007/s40262-017-0540-6. [Epub ahead of print]
Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.
Brown RT1, Nicholas CR1, Cozzi NV2, Gassman MC3, Cooper KM3, Muller D4, Thomas CD1, Hetzel SJ5, Henriquez KM3, Ribaudo AS3, Hutson PR6.
Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults.
Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods.
No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied.
The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose.
J Psychoactive Drugs. 2017 May 8:1-10. doi: 10.1080/02791072.2017.1320734. [Epub ahead of print]
Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders.
Thomas K1, Malcolm B2, Lastra D3.
Recent research suggests that functional connectivity changes may be involved in the pathophysiology of psychiatric disorders. Hyperconnectivity in the default mode network has been associated with psychopathology, but psychedelic serotonin agonists like psilocybin may profoundly disrupt these dysfunctional neural network circuits and provide a novel treatment for psychiatric disorders. We have reviewed the current literature to investigate the efficacy and safety of psilocybin-assisted therapy for the treatment of psychiatric disorders. There were seven clinical trials that investigated psilocybin-assisted therapy as a treatment for psychiatric disorders related to anxiety, depression, and substance use. All trials demonstrated reductions in psychiatric rating scale scores or increased response and remission rates. There were large effect sizes related to improved depression and anxiety symptoms. Psilocybin may also potentially reduce alcohol or tobacco use and increase abstinence rates in addiction, but the benefits of these two trials were less clear due to open-label study designs without statistical analysis. Psilocybin-assisted therapy efficacy and safety appear promising, but more robust clinical trials will be required to support FDA approval and identify the potential role in clinical psychiatry.
Note - This potential therapy is still in its infancy. Very few articles even considered the use of multi dosing which would limit the side effects and tolerance issues and yet still produce beneficial uses.
Posted 29 October 2017 - 01:32 PM
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