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Therapeutic Application

Capturing the different health conditions that PAP may adress

Serotonergic Hallucinogens and Emerging Targets for Addiction Pharmacotherapies

June 1, 2012 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

• Converging lines of evidence from pharmacologic, electrophysiologic, and behavioral
research in animals strongly suggest that activation of cortical 5-hydroxytryptamine-2A
receptors is the most critical step in initiating a cascade of biological events that accounts
for serotonergic hallucinogen (SH) psychoactive properties.
• Psilocybin produces hyperfrontality with divergent prefrontal–subcortical activation in such
a way as to increase cognitive and affective processing in the context of reduced gating
and reduced focus on external stimulus processing.
• In contrast to all other drugs of abuse, SHs are not considered to be capable of producing
sufficient reinforcing effects to cause dependence (addiction) syndromes.
• Given that SHs increase extracellular glutamate levels and activity in the prefrontal–
limbic circuitry, it is possible that a normalization in functional connectivity in this
network through a glutamate-dependent neuroplastic adaptation could produce an
anti-addictive effect.

Ross, S. (2012). Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies. Psychiatric Clinics of North America, 35(2), 357-374. http://dx.doi.org/10.1016/j.psc.2012.04.002
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LSD effective in the treatment of alcohol addiction

December 6, 2021 / LSD, Publications, Substance Use Disorder / By

alcoholismLSD can be effective in the treatment of alcoholism, according to a new study of a Norwegian research team. This study, published in the Journal of Psychopharmacology, shows that administration of LSD in alcoholics can contribute to the success of the treatment.

In this meta-analysis, the results of six randomized clinical trials that were published between 1966 and 1970 were used. In these studies LSD was administered in a total of 325 cases, and a placebo in 211 cases. Of the patients that received LSD 59% percent improved during the treatment, compared to only 38% of the persons receiving a placebo. The researchers conclude that there is evidence for a positive effect of LSD in the treatment of alcoholism.

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

March 8, 2012 / LSD, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36–2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

Krebs, T. S., & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(2), 994-1002. http://dx.doi.org/10.1177/0269881112439253
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Replication of Ketamine's Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial

January 31, 2012 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background

Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample.

Methods

In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion.

Results

Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61–1.16, and .98, 95% confidence interval = .64–1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point.

Conclusion

This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.

Zarate Jr., A., Brutsche, N. E., Ibrahim, L., Franco-Chaves, J., Diazgranados, N., Cravchik, A., … Luckenbaugh, D. A. (2011). Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial. Biological Psychiatry, 71(11), 939-946. http://dx.doi.org/10.1016/j.biopsych.2011.12.010
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Could MDMA be useful in the treatment of post-traumatic stress disorder?

December 15, 2011 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By /

Abstract

In recent studies, 3,4-methylenedioxymethylamphetamine (MDMA) has shown promise in the treatment of post-traumatic stress disorder (PTSD) as an adjunct to post-trauma psychological therapy. However, because of historical associations with its use as the recreational drug ecstasy, MDMA research remains a controversial subject. Dr Sessa discusses these controversies and describes a UK-based MDMA/PTSD currently in development.

Sessa, B. (2011). Could MDMA be useful in the treatment of post-traumatic stress disorder? Progress in Neurology and Psychiatry, 15(6), 4–7. http://dx.doi.org/10.1002/pnp.216
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Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

September 8, 2011 / Ketamine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.

Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V., Romanova, T. N., Slavina, T. Y., & Grinenko, A. Y. (2007). Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence. Journal of psychoactive drugs, 39(1), 13-19. https://dx.doi.org/10.1080/02791072.2007.10399860
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MDMA-Assisted Psychotherapy Using Low Doses in a Small Sample of Women with Chronic Posttraumatic Stress Disorder

September 8, 2011 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , ,

Abstract

The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.

Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. Á., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. Journal of psychoactive drugs, 40(3), 225-236., 10.1080/02791072.2008.10400637
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Combating substance abuse with ibogaine: pre- and posttreatment recommendations and an example of successive model fitting analyses

September 7, 2011 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Ibogaine is an indole alkaloid derived from the root bark of the African shrub Tabernan the iboga and it has been used for many years as a medicinal and ceremonial agent in West Central Africa. Furthermore, both anecdotal observations and recent studies suggest that ibogaine alleviates withdrawal symptoms and reduces drug cravings. Although ibogaine articles typically include information bearing on the duration of drug abstinence following treatment, little if any attention is given to the psychological and environmental factors that might facilitate a positive treatment outcome. Hence, a major purpose of the present review is to suggest a number of theory-driven, pretreatment and posttreatment recommendations that have good potential for enhancing ibogaine’s effectiveness. The second major purpose of this review is to demonstrate, through a reanalysis of previously published results, the utility of conducting successive model fitting analyses on ibogaine treatment data. Such analyses are useful for determining both the strength and form of the association between pre-ibogaine treatment variables and post-ibogaine treatment outcomes. Finally, in order to facilitate future quantitative reviews, the authors recommend that a minimum set of patient- and treatment-related variables be included in all ibogaine publications involving human participants.

Hittner, J. B., & Quello, S. B. (2004). Mechanisms of antiaddictive actions of ibogaine. Journal of Psychoactive Drugs, 36(2), 191-199. http://dx.doi.org/10.1080/02791072.2004.10399729
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A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department

September 1, 2011 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / ,

Abstract

We examined the preliminary feasibility, tolerability and efficacy of single-dose, intravenous (i.v.) ketamine in depressed emergency department (ED) patients with suicide ideation (SI). Fourteen depressed ED patients with SI received a single i.v. bolus of ketamine (0.2 mg/kg) over 1–2 min. Patients were monitored for 4 h, then re-contacted daily for 10 d. Treatment response and time to remission were evaluated using the Montgomery–Asberg Depression Rating Scale (MADRS) and Kaplan–Meier survival analysis, respectively. Mean MADRS scores fell significantly from 40.4 (S.E.M.=1.8) at baseline to 11.5 (S.E.M.=2.2) at 240 min. Median time to MADRS score f10 was 80 min (interquartile range 0.67–24 h). SI scores (MADRS item 10) decreased significantly from 3.9 (S.E.M.=0.4) at baseline to 0.6 (S.E.M.=0.2) after 40 min post-administration ; SI improvements were sustained over 10 d. These data provide preliminary, open-label support for the feasibility and efficacy of ketamine as a rapid-onset antidepressant in the ED.

Larkin, G. L., & Beautrais, A. L. (2011). A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. International Journal of Neuropsychopharmacology, 1127-1131. http://dx.doi.org/10.1017/S1461145711000629

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Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain

August 1, 2011 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

A growing body of evidence has pointed to the N-methyl-d-aspartate (NMDA) receptor antagonists as a potential therapeutic target for the treatment of major depression. The present study investigated the possibility of synergistic interactions between antidepressant imipramine with the uncompetitive NMDA receptor antagonist ketamine. Wistar rats were acutely treated with ketamine (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) and then subjected to forced swimming tests. The cAMP response element bindig (CREB) and brain-derived neurotrophic factor (BDNF) protein levels and protein kinase C (PKC) and protein kinase A (PKA) phosphorylation were assessed in the prefrontal cortex, hippocampus and amygdala by imunoblot. Imipramine at the dose of 10 mg/kg and ketamine at the dose of 5 mg/kg did not have effect on the immobility time; however, the effect of imipramine (10 and 20 mg/kg) was enhanced by both doses of ketamine. Ketamine and imipramine alone or in combination at all doses tested did not modify locomotor activity. Combined treatment with ketamine and imipramine produced stronger increases of CREB and BDNF protein levels in the prefrontal cortex, hippocampus and amygdala, and PKA phosphorylation in the hippocampus and amygdala and PKC phosphorylation in prefrontal cortex. The results described indicate that co-administration of antidepressant imipramine with ketamine may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whilst limiting side effects.

Réus, G. Z., Stringari, R. B., Ribeiro, K. F.,  Ferraro, A. K.,  Vitto, M. F., Cesconetto, P., … Quevedo, J. (2011). Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain. Behavioural Brain Research, 221(1), 166-171. http://dx.doi.org/10.1016/j.bbr.2011.02.024
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