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Psychology

Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects

May 27, 2017 / MDMA, Papers, Psychology / By / , , , ,

Abstract

Rationale

3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally and investigated as an adjunct to psychotherapy. Methylphenidate and modafinil are psychostimulants that are used to treat attention-deficit/hyperactivity disorder and narcolepsy, respectively, but they are also misused as cognitive enhancers. Little is known about differences in the acute effects of equally cardiostimulant doses of these stimulant-type substances compared directly within the same subjects.

Methods

We investigated the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg), and placebo in a double-blind, cross-over study in 24 healthy participants. Acute drug effects were tested using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI).

Results

All active drugs produced comparable hemodynamic and adverse effects. MDMA produced greater increases in pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness than methylphenidate or modafinil. Only MDMA reduced subjective anxiety and impaired fear recognition and led to misclassifications of emotions as happy on the FERT. On the SADI, only MDMA produced sexual arousal-like effects. Only MDMA produced marked increases in cortisol, prolactin, and oxytocin. In contrast to MDMA, methylphenidate increased subjective anxiety, and methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT. Modafinil had no significant subjective drug effects but significant sympathomimetic and adverse effects.

Conclusions

MDMA induced subjective, emotional, sexual, and endocrine effects that were clearly distinct from those of methylphenidate and modafinil at the doses used.

Dolder, P. C., Müller, F., Schmid, Y., Borgwardt, S. J., & Liechti, M. E. (2017). Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects. Psychopharmacology, 1-13. 10.1007/s00213-017-4650-5
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Psilocybin: Good Trip or Bad Trip

May 26, 2017 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Much of the history of pharmacology and therapeutics involves finding new uses for old drugs. The latest rediscovery is that of psychedelic drugs.[1] Since they can cause profound distortions of perception and were once used as part of religious ceremonies, such research may seem unusual at this time.
Sellers, E. M. (2017). Psilocybin: Good Trip or Bad Trip. Clinical Pharmacology & Therapeutics. 10.1002/cpt.697
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Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

May 25, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

BACKGROUND:
Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine.
OBJECTIVES:
To study outcomes following opioid detoxification with ibogaine.
METHODS:
In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively.
RESULTS:
SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all posttreatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month.
CONCLUSION:
Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.
Brown, T. K., & Alper, K. (2017). Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse, 1-13. 10.1080/00952990.2017.1320802
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Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

May 23, 2017 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Philosophy & Religious Studies, Psychology, Publications / By /

Abstract

There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED.
Millière, R. (2017). Looking For The Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution. Frontiers in Human Neuroscience, 11. 10.3389/fnhum.2017.00245
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Therapeutic Applications of Classic Hallucinogens

May 18, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.
Bogenschutz, M. P., & Ross, S. (2016). Therapeutic applications of classic hallucinogens. 10.1007/7854_2016_464
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Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile

May 18, 2017 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
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Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile

May 18, 2017 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
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Associations between Specific Dissociative Symptoms and Symptom Subsets and Anti-Depressant Response to Ketamine

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , ,

Abstract

Ketamine has been shown to produce rapid antidepressant effects in major depression and bipolar disorder. Due to ketamine’s glutamatergic properties, many patients report dissociative effects, which recent studies have shown to be associated with increased anti-depressant response. Thus we investigated the connection between distinct subscales of dissociation and differing treatment response.

Shovestul, B., Jaso, B., Luckenbaugh, D., Park, L., Niciu, M., & Zarate, C. (2017). 199-Associations between Specific Dissociative Symptoms and Symptom Subsets and Anti-Depressant Response to Ketamine. Biological Psychiatry, 81(10), S82-S83. 10.1016/j.biopsych.2017.02.212
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Ketamine as a Treatment for Adolescent Major Depressive Disorder

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , ,

Abstract

Nearly 1 in 4 adolescents will experience major depressive disorder (MDD). Suicide is the 3rd leading cause of death in this age group. 40% of adolescents with MDD fail to respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs). Of that SSRI-resistant population, nearly half remain depressed despite alternate medication and psychotherapy. Thus, better treatments for adolescent depression are urgently needed. Subanesthetic doses of ketamine, an NMDA antagonist, produce rapid antidepressant and anti-suicidal effects in depressed adults. There are few case reports and no prospective controlled trials of ketamine for the treatment of adolescent MDD.

Dwyer, J., Sanacora, G., & Bloch, M. (2017). 1002-Ketamine as a Treatment for Adolescent Major Depressive Disorder. Biological Psychiatry, 81(10), S405. 10.1016/j.biopsych.2017.02.729
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Clinical Predictors of an Antisuicidal Response to Ketamine

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Suicide is one of the leading causes of death in the United States. Despite treatment efforts, the national suicide rate has increased in recent years. Currently, there are no pharmacological treatments for suicidal ideation (SI). For individuals experiencing a suicidal crisis, rapid acting medications may save lives. Recent studies suggest ketamine, a glutamate modulator, elicits rapid antisuicidal responses. We examined clinical factors that might predict ketamine’s antisuicidal response as a step towards understanding ketamine’s mechanism of action on suicidal thoughts.

Yarrington, J., Ballard, E., Luckenbaugh, D., Niciu, M., Lener, M., Kadriu, B., … & Zarate, C. (2017). 1004-Clinical Predictors of an Antisuicidal Response to Ketamine. Biological Psychiatry, 81(10), S406. 10.1016/j.biopsych.2017.02.731
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