4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence ...of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.
Background: Tissue engineering using mesenchymal stem cells (MSCs) is a recent therapeutic modality that has several advantages. MSCs have high proliferation potential and may be manipulated to ...permit differentiation before being transplanted, suggesting they may be an ideal candidate for regenerative procedures. Precise identification of cells capable of regenerating the periodontium is valuable because no predictable regeneration procedure has yet been described. The purpose of this study is to determine the presence of MSCs in human gingival connective tissue and their morphologic and functional characteristics.
Methods: Gingival connective tissue samples were obtained from five healthy students. The samples were deepithelialized, leaving only connective tissue. The explants were minced and cultured on tissue culture dishes for 3 to 4 weeks, after which cells were characterized by flow cytometry. Differentiation into osteogenic, chondrogenic, and adipogenic lineages was induced and evaluated by culture staining. An immunoregulation assay was also performed.
Results: The results show that gingival tissue cells fulfill the minimal criteria proposed by the International Society for Cellular Therapy to be defined as MSCs. Cell characterization was consistently positive for CD90, CD105, CD73, CD44, and CD13 markers and negative for hematopoietic markers CD34, CD38, CD45, and CD54. We observed differentiation in positive staining of adipogenic, chondrogenic, and osteogenic lineages. Furthermore, gingival cells showed immunomodulative capacity.
Conclusion: Gingival connective tissue could be a reservoir of MSCs that could be used in regenerative procedures based on tissue engineering.
Sustainable procurement and supply chain management studies are growing; however several scholars have criticised the lack of theoretical development accompanying this literature. Sustainable ...procurement and supply chain management activities form part of an organisation's path to adopt sustainability. Some scholars have suggested examining the application of management theories to describe the introduction of corporate sustainability to address this gap. Institutional theory is frequently used to describe how new practices are adopted in organisations and has also been applied to several corporate social responsibility studies. This conceptual paper examines the applicability of institutional theory to describe the adoption of sustainable procurement and concludes by presenting three theoretical propositions to explain sustainable procurement adoption.
Age-related macular degeneration (AMD) is a leading cause of visual impairment in aging populations in industrialized countries. Here we investigated whether the genotype of vascular endothelial ...growth factor A (VEGFA) gene is associated with response to anti-VEGF therapy. 223 eyes with neovascular AMD were treated with intravitreal anti-VEGF therapy. Responders were defined as patients who had an improvement in best corrected visual acuity (BCVA) of at least 5 letters or one line on the EDTRS visual acuity chart along with resolution of intraretinal or subretinal fluid over 12 months. Patients who did not meet the definition of responders were classified as poor-responders. The vision of responders (n = 148) improved while the vision of poor-responders (n = 75) worsened (P<0.001). Responders on average had a decrease in central foveal thickness (CFT), while poor-responders had an increase in CFT (P <0.001). Compared with the responder group, the poor-responder group had a higher frequency of the risk (T) allele (Allelic P = 0.019) and TT genotype (P = 0.002 under a recessive model) for the VEGFA-rs943080 polymorphism. VEGFA expression was 1.8-fold higher in cells with the VEGFA rs943080 TT genotype than in cells with the VEGFA rs943080 CC genotype (P = 0.012). Age, gender, smoking, diabetes mellitus, and hypertension did not play a significant role in treatment response, but BMI was found to be significantly different between responders and poorresponders (P = 0.033). In conclusion, we demonstrated a potential pharmacogenetic relationship between the VEGFA gene and treatment response to anti-VEGF therapy.The studies are registered at ClinicalTrials.gov under the identifiers NCT00474695 (http://clinicaltrials. gov/ct2/show/NCT00474695) and NCT01464723 (http://clinicaltrials.gov/ct2/show/NCT01464723).
Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects ...infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities.
1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g SD=2,788 and last use a mean of 4.9 months earlier SD=6.0; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g SD=16,850 and last use a mean of 6.3 months earlier SD=7.8; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia.
HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%).
The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.
Rationale
Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise ...as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted.
Objectives
To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population.
Methods
Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg,
n
= 8) or inactive placebo (0 mg,
n
= 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session.
Results
Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (
P
= 0.037), and placebo-subtracted Cohen’s
d
effect size was very large (
d
= 1.4, CI − 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (
P
= 0.036), with a Cohen’s
d
effect size of 1.1 (CI − 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase.
Conclusions
This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety.
Trial registration
clinicaltrials.gov
identifier, NCT02008396
Is LSD toxic? Nichols, David E.; Grob, Charles S.
Forensic science international,
March 2018, 2018-Mar, 2018-03-00, 20180301, Letnik:
284
Journal Article
Recenzirano
•LSD has rarely been associated with accidental deaths and suicide.•LSD is known to be non-toxic and physiologically safe when used at moderate dosages.•Death attributed to LSD toxicity appear in ...conjunction only with maximal restraint.•Forensic investigators should understand the true causes of LSD-related fatalities.
LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD’s potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50–200μg). The scientific literature, along with recent media reports, have unfortunately implicated “LSD toxicity” in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD.
Background: New Mexico was the first state to list post-traumatic stress disorder (PTSD) as a condition for the use of medical cannabis. There are no published studies, other than case reports, of ...the effects of cannabis on PTSD symptoms. The purpose of the study was to report and statistically analyze psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico Medical Cannabis Program from 2009 to 2011. Methods: The Clinician Administered Posttraumatic Scale for DSM-IV (CAPS) was administered retrospectively and symptom scores were then collected and compared in a retrospective chart review of the first 80 patients evaluated. Results: Greater than 75% reduction in CAPS symptom scores were reported when patients were using cannabis compared to when they were not. Conclusions: Cannabis is associated with reductions in PTSD symptoms in some patients, and prospective, placebo-controlled study is needed to determine efficacy of cannabis and its constituents in treating PTSD.
PDF
