Disrupting Memories of Cocaine Use Might Prevent Relapse

May 17, 2017 · Posted in Potential Treatments · Comment 

cocaine treatment

Cocaine users who want to abstain from the drug may find that encountering people or places who remind them of past cocaine use can increase their cravings for the drug and lead to relapse. Researchers are studying animals to see if disrupting the link between an environmental cue and the memory of cocaine’s effects could reduce cravings for the drug.

In a 2016 article in the journal Neuropsychopharmacology, researcher Melissa S. Monsey and colleagues reported that in rats, the amnesia-causing natural compound garcinol can weaken the cues that lead to a cocaine-seeking. Garcinol is derived from the rind of kokum (or Garcinia indica) fruit, which is native to the west coast of India.

Monsey and colleagues delivered the garcinol during a period when the rats’ brains were reconsolidating memories that linked an environmental cue with the pleasurable effects of cocaine.

For 12 days, the rats in the study could press a lever and receive an intravenous infusion of cocaine that was paired with a light and a sound. Then the lever stopped working for 8 days. Next, the researchers observed how the rats behaved when the light and sound returned.

The light and sound were meant to remind the rats of the previous times they received cocaine, prompting their brains to reconsolidate the memory linking the light/sound with the pleasurable effects of cocaine.

Half of the rats were given an injection of garcinol during this memory reconsolidation period. While all of the rats continued to seek out cocaine, in the garcinol-treated rats, the light/sound was no longer linked to cocaine. Their cocaine-seeking behavior from then on was unrelated to the light/sound, and the link between the light/sound and cocaine could not be reinstated in these rats.

This research on rats may help clarify how cravings are produced in the brain, and how they might be prevented or treated.

Editor’s Note: In 2012, Yan-Xue Xue and colleagues reported in the journal Science that in humans, psychological techniques can be used to help a patient unlearn the association between an environmental cue and the effects of a drug, using the same theory of the memory reconsolidation period. When patients in recovery from heroin addiction were prompted to revisit memories of heroin use 10 minutes before extinction training (in which they looked at heroin or heroin paraphernalia without receiving the drug), they ended up with fewer cravings for heroin 1, 30, and 180 days later compared to patients who did extinction training without revisiting memories of past heroin use (and thus without opening the memory reconsolidation window, which researchers believe opens 5 minutes to an hour after someone engages in active recall).

National Academy of Sciences, Engineering and Medicine Issues Report on the Health Effects of Cannabis

May 8, 2017 · Posted in Potential Treatments, Resources, Risk Factors · Comment 

The Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for ResearchIn early 2017, the National Academy of Sciences, Engineering, and Medicine issued its first comprehensive report on cannabis since 1999. Shifting public opinion over the past few decades has led to 28 states and the District of Columbia legalizing medical uses of marijuana, and eight states and DC legalizing recreational marijuana use. The Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for Research is intended to address the lack of accepted standards to guide individuals in deciding whether and how to use cannabis safely. In addition to summarizing recent health-related findings on cannabis, the report also offers recommendations to guide future research.

The report shares findings about possible therapeutic benefits to cannabis use as well as health impacts relating to areas such as cancer, respiratory disease, immunity, pre- and post-natal health.

There were several notable findings with regard to mental health. The committee that issued the report found substantial evidence of a statistical association between cannabis use and the development of schizophrenia or other psychoses, with the highest risk among the most frequent users.

The committee also found moderate evidence of a link between cannabis use and increased symptoms of mania and hypomania in people with bipolar disorder who use cannabis regularly. The report also describes moderate evidence of an association between heavy cannabis use and increased suicidal ideation and suicide attempts.

There was also moderate evidence that regular cannabis use is linked to social anxiety disorder.

The report described factors that may lead to problem cannabis use. The committee found substantial evidence that being male, smoking cigarettes, and beginning cannabis use at an earlier age are risk factors for developing problem cannabis use. Read more

Melatonin May Improve Headaches

April 27, 2017 · Posted in Potential Treatments · Comment 

young woman suffering from headache

A 2016 article in the Journal of Head and Face Pain reviewed randomized placebo-controlled trials of melatonin for the treatment of headaches. Author Amy A. Gelfand and colleagues reported that 10 mg of melatonin was superior to placebo in the treatment of cluster headaches. For treatment of migraines, 3 mg of immediate-release melatonin improved headaches compared to placebo, while 2 mg of sustained-release melatonin was insufficient.

The authors also found non–placebo controlled data suggesting that melatonin may be helpful for other types of headaches. More research is needed to clarify melatonin’s effects in different headache disorders.

Immune Therapy with IVIG May Help Children with PANDAS

April 26, 2017 · Posted in Potential Treatments · Comment 

Healthy girl after IVIGA small number of children exposed to streptococcal bacteria have an autoimmune response that manifests in sudden, severe obsessive-compulsive behaviors and tics. This disorder is known as PANDAS: pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection, and it resembles the broader disorder PANS, which can occur after other types of bacterial or viral infections.

Research on treatments for PANDAS and PANS is scant, but therapies that target the immune system seem to have more success than typical psychiatric treatments. In a 2015 article in the Journal of Child and Adolescent Psychiatry, researcher Miro Kovacevic and colleagues described a case series of 12 youths with PANDAS who were treated with intravenous immunoglobin (IVIG), a treatment designed to regulate the immune system. (The participants also met diagnostic criteria for PANS.)

The authors suggest that PANDAS symptoms result from a misdirected immune response that attacks the patient’s brain instead of or in addition to attacking the initial infection. IVIG treatment uses a mixture of antibodies from about 1,000 people. When this mixture is infused into the patient’s blood, the antibodies help deflect the autoimmune attack on the patient’s body. All of the 12 patients had a good long-term response to IVIG. Some did well after just one infusion, while two needed a second infusion because they did not respond to the first, and five had recurring symptoms that required a second infusion. All of the patients had previously received two other types of treatment: a 5-day course of steroids and antibiotics, neither of which produced immediate improvements.

The authors concluded that effective long-term treatment of PANS or PANDAS should combine immune therapy, prevention of future infections with antibiotics, and treatment that targets their psychiatric symptoms, such as anti-obsessional medication or cognitive-behavioral therapy.

Combo of Memantine and Sertraline Effective for Unipolar Depression

April 13, 2017 · Posted in Potential Treatments · Comment 

Content young woman lying on couch

A 2016 study in the Journal of Clinical Pharmacy and Therapeutics finds that the combination of memantine (Namenda), a drug used to treat Alzheimer’s disease, and the antidepressant sertraline (Zoloft) improved unipolar depression more than sertraline plus placebo.

The study by Meysam Amidfar and colleagues included 66 patients with moderate to severe unipolar depression. They were divided into two groups—one received sertraline plus memantine for six weeks, while the other received sertraline and a placebo.

The memantine group showed significantly greater improvement at 2 weeks, 4 weeks, and 6 weeks, and significantly greater response at 4 and 6 weeks. There were also more early improvers in the mematine group, and more rapid response to treatment. Both groups improved significantly over the six weeks of treatment.

Larger studies are needed to learn more about the safety and efficacy of memantine combined with sertraline for the treatment of unipolar depression, but this initial study is promising. In 2012, researcher Amit Anand and colleagues reported that in bipolar depression, memantine potentiates the effects of lamotrigine. Memantine also helped rapid cyclers when added to ongoing treatment in an open study of the drug treatment by Athanasios Koukopoulus and colleagues in 2012.

Supplement Acetyl-L-Carnitine May Treat Stress and Depression

April 7, 2017 · Posted in Potential Treatments · Comment 

stressed woman

N-acetylcysteine (NAC), an antioxidant sold in health food stores, has several beneficial effects on brain and behavior. It improves depression and can reduce cravings for cocaine, alcohol, marijuana, and nicotine, and can also help control habit-driven behaviors such as gambling, compulsive hair-pulling, and symptoms of obsessive-compulsive disorder (OCD).

New research, particularly by researcher Nascaa and colleagues in 2014 and 2016, has identified a related compound, acetyl-l-carnitine (ALC), as an anti-stressor and antidepressant in animals, and researchers have begun to explore its use in people. ALC has been found to improve mitochondrial function and improve recovery from peripheral nerve damage. ALC also inhibits the release of glutamate, which can prevent depressive behaviors following stress.

A 2004 study by P. Ruggenenti and colleagues in the journal Hypertension found that in people, 1 gm of ALC taken twice daily safely improved arterial hypertension, insulin resistance, impaired glucose tolerance, and low levels of adiponectin in the blood (a risk factor for diabetes) in subjects at increased cardiovascular risk.

In a 2014 article in the Journal of Psychiatric Research, researcher S.M. Wang and colleagues reviewed evidence that ALC improves mild depression. Two randomized clinical trials indicated that ALC was more effective than placebo for mild depression. Two other randomized clinical trials showed that ALC was as effective as the antidepressants fluoxetine and amisulpride for mild depression. The supplement was as tolerable as placebo and better tolerated than fluoxetine and amisulpride. Wang and colleagues suggested that more clinical trials are needed to confirm that ALC is effective in depression.

Editor’s Note: If further clinical trials confirm the antidepressant effects of ALC, it could represent a new way to treat chronic stress and depression and regulate insulin. Together these effects could reduce the cardiovascular risks that accompany depression.

Arthritis Drug Celecoxib May Improve Bipolar Depression When Paired with Escitalopram

March 13, 2017 · Posted in Potential Treatments · Comment 

celecoxib combined with escitalopram for bipolar depression

A new study suggests that for people with bipolar depression, the anti-inflammatory drug celecoxib (Celebrex), typically used to treat arthritis, can boost the effectiveness of the antidepressant escitalopram (Lexapro).

In the 8-week study by researcher Angelos Halaris and colleagues, adults with bipolar depression were randomly assigned to one of two groups. The first group received the selective-serotonin reuptake inhibitor (SSRI) antidepressant escitalopram plus celecoxib to target inflammation. The second group received just the antidepressant escitalopram and a placebo.

By the end of the study, 78% of the group taking the anti-arthritis drug had seen major improvement in their depression, with 63% reporting that it had lifted completely. Meanwhile in the placebo group, only 45% reported major improvement, and 10% reported remission.

The group that received celecoxib with their escitalopram also began seeing improvement within one week of beginning treatment, instead of after four to six weeks, which is typical of antidepressant treatment.

Researchers think depression creates an immune response leading to chronic inflammation, which can upset the balance of neurotransmitters in the brain and make antidepressants less effective. Halaris suggests that reducing this inflammation with a drug like celecoxib can make antidepressants more effective.

The research was presented at the Fifth International Congress on Psychiatry and the Neurosciences and has not yet been published.

Anti-Inflammatory Treatments Improve Depression

March 9, 2017 · Posted in Potential Treatments · Comment 
Tumor necrosis factor

Tumor necrosis factor

Inflammation can interfere with the balance of neurotransmitters in the brain, making antidepressants less effective. Anti-inflammatory treatments (such as those used to treat rheumatoid arthritis) may help. In a 2016 meta-analysis published in the journal Molecular Psychiatry, researchers led by Nils Kappelmann analyzed the results of 20 clinical trials of chronic inflammatory conditions where depressive symptoms were also recorded. In a subset of 7 clinical trials that compared anti-inflammatory treatment to placebo, they found that anti-inflammatory treatment improved depressive symptoms significantly compared to placebo.

The anti-inflammatory drugs studied most often targeted the inflammatory marker tumor necrosis factor (TNF) alpha using an antibody. Some of the anti-inflammatory drugs that improved depressive symptoms were adalimumab, etanercept, infliximab, and tocilizumab.

The researchers also found that those participants with the most inflammation when they began treatment saw the largest improvement in their depression after taking anti-inflammatory treatments.

Kappelmann and colleagues suggest that inflammation may cause depression, and that anti-inflammatory drugs may be useful in the treatment of depression in people with high inflammation.

Vitamin D Supplementation May Not Be Effective in Bipolar Depression, But Is Still Worth Doing

January 27, 2017 · Posted in Potential Treatments · Comment 

vitamin DIn some studies, vitamin D supplementation (1,500 IU/day) has been found to improve unipolar depression. Recently, researchers led by Wendy K. Marsh found that compared to placebo, 12 weeks of vitamin D3 supplementation (5,000 IU/day) did not produce greater improvement in depressive symptoms. The study, presented at the 2016 meeting of the Society of Biological Psychiatry, included 33 adult participants whose vitamin D levels remained deficient throughout the study.

Editor’s Note: Caution is urged in interpreting this small study, especially because the participants did not achieve healthy levels of vitamin D.

Low levels of vitamin D are common in children and adults with bipolar disorder. Future research may explore whether raising vitamin D levels to healthy levels has a beneficial effect on mood. There are many other benefits to vitamin D supplementation. It can improve cognition, regulate calcium and phosphorus absorption, and maintain healthy bones and teeth. It may also protect against diseases such as cancer, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. Improved cardiovascular health is also a possible benefit of vitamin D supplementation.   

Omega-3 Fatty Acids May Be Helpful Early in Schizophrenia, But Not Later

January 24, 2017 · Posted in Potential Treatments · Comment 

sources of omega-3 fatty acidsSome studies have suggested that omega-3 fatty acids may be helpful in the treatment of schizophrenia, but data to support this idea have been inconsistent. A recent meta-analysis of research on omega-3s and schizophrenia suggests that this nutritional supplement might be more useful in early-stage schizophrenia than in later illness.

At the 2016 meeting of the Society of Biological Psychiatry, researchers led by Alexander T. Chen presented the findings of their meta-analysis. First they analyzed six studies that shared a common scale for measuring schizophrenia symptoms. In these studies, omega-3 fatty acids did not outperform placebo when used as an add-on treatment to antipsychotics for people with schizophrenia.

In four remaining studies of omega-3 fatty acids and schizophrenia, the omega-3s were associated with improvement only in patients in the early stages of schizophrenia. Compared to placebo, the supplements decreased non-psychotic symptoms, decreased the dosage of antipsychotic medication patients required, and improved early treatment response (but not late treatment response) in patients in their first episode of schizophrenia.

In the same study, omega-3 fatty acids also reduced conversion to full-blown schizophrenia and psychotic symptom severity in patients at high risk for schizophrenia who were having preliminary symptoms of the illness.

Editor’s Note: Researcher Paul E. Keck has also found that omega-3 fatty acids may be more effective early in bipolar disorder rather than later. He reported that younger patients with bipolar depression and rapid cycling showed more improvement when taking the omega-3 fatty acid EPA than when taking placebo. In contrast, patients with bipolar depression who were over the age of 45 did worse on EPA than on placebo.

Part of the ambiguity about whether omega-3 fatty acids can help treat or prevent mental illness may be explained by the supplements working better in younger people or earlier in the course of an illness.

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