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Ketamine for major depression: New tool, new questions

Ketamine was once used mainly as an anesthetic on battlefields and in operating rooms. Now this medication is gaining ground as a promising treatment for some cases of major depression, which is the leading cause of disability worldwide. In the US, recent estimates show 16 million adults had an episode of major depression in the course of a year. Suicide rates rose substantially between 1999 and 2016, increasing by more than 30% in 25 states. Because of its rapid action, ketamine could have a role to play in helping to prevent suicide.

Why is ketamine exciting for treating depression?
If a person responds to ketamine, it can rapidly reduce suicidality (life-threatening thoughts and acts) and relieve other serious symptoms of depression. Ketamine also can be effective for treating depression combined with anxiety.

Other treatments for suicidal thoughts and depression often take weeks or even months to take effect, and some people need to try several medications or approaches to gain relief. This is true for talk therapies, antidepressant medicines, transcranial magnetic stimulation (TMS), and electroconvulsive therapy (ECT), which is currently the most effective treatment for major depression that fails to respond to other therapies.

Are there different types of ketamine?
Two main types of ketamine are used to treat major depression that hasn’t responded to two or more medications (treatment-resistant depression).

Racemic ketamine, which is most often given as an infusion into the bloodstream. This is sometimes called intravenous, or IV, ketamine. It is a mixture of two mirror-image molecules: “R” and “S” ketamine. While it was approved decades ago as an anesthetic by the FDA, it is used off-label to treat depression.
Esketamine (Spravato), which the FDA approved in March, is given as a nasal spray. It uses only the “S” molecule.
Thus far, most research has been on ketamine infusions.

The two forms of ketamine interact differently with receptors in the brain. The delivery of ketamine and the type given affect drug effectiveness and side effects. We don’t yet know which type is more effective or how much side effects may differ. Further research comparing effectiveness and side effects is needed.

How does ketamine work?
It’s not entirely clear how ketamine works. Because it exerts an antidepressant effect through a new mechanism, ketamine may be able to help people successfully manage depression when other treatments have not worked.

One likely target for ketamine is NMDA receptors in the brain. By binding to these receptors, ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons. Glutamate then activates connections in another receptor, called the AMPA receptor. Together, the initial blockade of NMDA receptors and activation of AMPA receptors lead to the release of other molecules that help neurons communicate with each other along new pathways. Known as synaptogenesis, this process likely affects mood, thought patterns, and cognition.

Ketamine also may influence depression in other ways. For example, it might reduce signals involved in inflammation, which has been linked to mood disorders, or facilitate communication within specific areas in the brain. Most likely, ketamine works in several ways at the same time, many of which are being studied.

What are the possible side effects of ketamine?
All drugs have side effects. When someone is suicidal or severely depressed, possible benefits may outweigh possible risks.

Ketamine given by infusion may cause:

high blood pressure
nausea and vomiting
perceptual disturbances (time appearing to speed up or slow down; colors, textures, and noises that seem especially stimulating; blurry vision)
dissociation (sometimes called out-of-body experiences); rarely, a person may feel as if they are looking down on their body, for example.
Generally, any changes in perception or dissociation are most noticeable during the first infusion and end very quickly afterward.

Esketamine nasal spray may cause the same side effects. However, the timing and intensity of those effects is different.

Long-term or frequent use of ketamine may have additional side effects. More research on this is needed.

What else should you know about ketamine?
A much lower dose of ketamine is given for depression compared with the dose necessary for anesthesia.
Like opioids, ketamine has addictive properties. It’s important to understand this when weighing risks and benefits. If you have a history of substance abuse –– such as alcohol or drugs –– it’s especially important for you and your doctor to consider whether ketamine is a good option for you.
When IV (racemic) ketamine works, people usually respond to it within one to three infusions. If a person has no response at all, further infusions are unlikely to help. Instead, it’s probably best to try other treatments for depression.
People who experience some relief from depression within one to three ketamine treatments are probably likely to extend these positive effects if the treatment is repeated several more times. The subsequent sessions may help prolong the effects of ketamine, rather than achieving further dramatic relief of symptoms. There are no standard guidelines for this. Many studies offer eight treatments initially (acute phase). After this, patient and doctor decide whether to taper or stop ketamine treatments, or continue treatments at longer intervals.

What You Need to Know About Ecstasy

In 2015, a 24-year-old man died after ingesting a fatal dose of the drug ecstasy at the Electric Daisy Carnival (EDC) in Las Vegas. This wasn’t the first time an ecstasy-related death made headlines, despite the fact that many users consider the popular substance a relatively safe recreational drug. But as droves of dance music enthusiasts and party-goers continue to head to festivals like EDC and Burning Man, it’s important to realize that ecstasy is not without risk.

Worldwide, ecstasy is as commonly used as cocaine, amphetamines, and opiates. Ecstasy combines the effects, both positive and negative, of amphetamines and many common antidepressants. The resultant euphoria, wakefulness, sexual arousal, disinhibition, and psychedelic effects are, after all, what attract users.

Most often taken as a pill, ecstasy can also be snorted, smoked, or ingested as a powder or crystalline form called “molly.” Because the pills are often adulterated with other drugs (e.g., marijuana or cocaine), many users believe that “molly” offers a purer alternative, but this is increasingly untrue. Molly, like other forms of ecstasy, is often cut with many different substances that users ingest unknowingly.

Side Effects of Ecstasy
Certain side effects of ecstasy are predictable and relatively minor, including loss of appetite, teeth grinding, and fever. Many users put pacifiers in their mouths, anticipating the teeth grinding, and many consume large quantities of fluids in an effort to limit the fever. Also, after the drug wears off, it’s common for users to feel tired, irritable, and depressed. The severity of these feelings varies from person to person.

Severe side effects are uncommon but may include:

Psychosis
Liver toxicity
Bleeding in the brain
Severe dehydration
Dangerously low levels of sodium in the bloodstream from drinking too much water
Fever that gets so high it can lead to muscle breakdown and kidney failure
Serotonin syndrome
Cardiac problems, including potentially fatal arrhythmias and heart attacks
Severe depression and suicidality
Putting the Dangers into Perspective
Exact statistics aren’t available, but fortunately, we know that dying due to ecstasy is highly unlikely. While it is possible to overdose on ecstasy, taken on its own, it rarely leads to death. To put the risk into perspective, there is a much higher likelihood of dying from drinking alcohol or smoking cigarettes.

Stay Safe
Given the variability of pre-existing health conditions, dosage, and the combination of substances that can all negatively impact a person’s experience, it’s difficult to categorically describe the risk of taking ecstasy. The safest action you can take is to avoid it altogether. However, if you have taken ecstasy or plan to take it, here are some steps you can take that may help reduce the severity of symptoms:

Stay hydrated. Ecstasy use is associated with both dehydration and over-hydration, both of which can be dangerous at extreme levels. Drink a moderate amount of water regularly–use thirst as your guide–and supplement it with salty snacks to keep your sodium levels normal. Alternatively, a sports drink (or any balanced electrolyte beverage) will allow you to hydrate adequately while maintaining normal sodium levels.
Catch up on sleep. If you plan to take ecstasy, make sure you’re well-rested before you take it, and don’t skimp on sleep afterward. Being well-rested will aid in recovery.
Don’t overexert yourself. Take care of your body as it readjusts to its normal state.
Don’t take ecstasy in high doses. It’s impossible to know the precise amount of ecstasy in any given dose of any preparation, whether pill or powder. And be aware that an ecstasy high may take up to an hour to kick in, so don’t take chances by taking another hit to intensify your high or delay the coming-down.
Don’t mix ecstasy with alcohol or other drugs. Most serious health problems related to ecstasy use are associated with ecstasy in combination with other substances, including alcohol and other drugs. Combining ecstasy with alcohol and other drugs increases your risk of something going wrong. Additionally, alcohol is a depressant and a diuretic, so avoid drinking alcohol after taking ecstasy, as it can impair your recovery process.
Know the source. Knowing where the drug came from may give you insight into whether it has been cut with other drugs, and how concentrated it is. Don’t take ecstasy from unknown or untrusted sources.
Future research might tell us more about the safety of ecstasy, and emerging technology might even enable users to test the purity of pills before taking them. In the meantime, like most other recreational drugs, ecstasy is a drug best avoided or used very sparingly.

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Malcolm Thaler, One Medical Provider
Malcolm enjoys being on the front lines of patient care, managing diagnostic and therapeutic challenges with a compassionate, integrative approach that stresses close doctor-patient collaboration. He is the author and chief editor of several best-selling medical textbooks and online resources, and has extensive expertise in managing a wide range of issues including the prevention and treatment of cardiovascular disease, diabetes, and sports injuries. Malcolm graduated magna cum laude from Amherst College, received his MD from Duke University, and completed his residency in Internal Medicine at Harvard’s New England Deaconess Hospital and Temple University Hospital. He joined One Medical from his national award-winning Internal Medicine practice in Pennsylvania and was an attending physician at The Bryn Mawr Hospital since 1986. He is certified through the American Board of Internal Medicine. Malcolm is a One Medical Group provider and sees patients in our New York offices.
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The One Medical blog is published by One Medical, an innovative primary care practice with offices in Boston, Chicago, Los Angeles, New York, Phoenix, the San Francisco Bay Area, Seattle, and Washington, DC.

Any general advice posted on our blog, website, or app is for informational purposes only and is not intended to replace or substitute for any medical or other advice. The One Medical Group entities and 1Life Healthcare, Inc. make no representations or warranties and expressly disclaim any and all liability concerning any treatment, action by, or effect on any person following the general information offered or provided within or through the blog, website, or app. If you have specific concerns or a situation arises in which you require medical advice, you should consult with an appropriately trained and qualified medical services provider.

DMT Drug: Uses and Risk

DMT is also known as Dimethyltryptamine. It’s a psychedelic drug that derives from plants found in South America, Asia, and Mexico. This natural plant extract has been used for centuries as a means of healing people. In the past, taking the drug would involve guides to help you through the trip to find the answers you were looking for. DMT has been labeled in more modern times as the “spirit molecule.” This is due to its powerful ability to allow users to connect to a deeper aspect of themselves. what is dmtIn the 1960s, DMT had many nicknames, one of them being the “businessman’s trip”. This was because DMT offered a high that was much shorter than LSD or other psychedelics. For those who didn’t have time for the twelve-hour high from acid, DMT was an alternative for a quick trip. It is also extremely intense. Advocates state that taking DMT can be a life-changing event as you tap into your undiscovered potential. It is strongly believed that DMT can help in the recovery of drug or alcohol addiction. DMT has a strong effect on the serotonin receptors that are involved with depression. Depression is a major reason people will begin self-medicating with substances. However, this is merely a theory that has yet to be studied in full.

Methods of Taking DMT
DMT can be inhaled, ingested, or taken orally. How you take it and how much you take will dictate what your trip will be like. Inhaling or injecting it will allow you to feel its effects for 5-15 minutes. This method is said to give you lightning fast images with a fast-moving trip. If you take the traditional ayahuasca brew (MAIO), it can last for three hours or longer. This trip is much slower and allows the brain to take in all the messages it’s receiving. consuming dmtAlone, DMT is usually not effective because of the MAO enzyme that breaks down chemicals. When MAO-inhibitors are added, it stops the breakdown of chemicals so you can feel high. These inhibitors need to be used by someone who is well informed of ratios in the doses. MAOI can cause food to become poisonous which can result in headaches, nausea, and potentially death. Traditionally, shamans will fast for one full day before using MAO-inhibitors. This is to prevent an interaction with food that’s been eaten. It can also prevent a person from vomiting during their trip.

What You Can Expect When You Take DMT
It’s been said that there is no real way to prepare you for the trip that DMT will take you on. You will have a mystical experience that is out of this world. It will seem like reality and you may experience euphoria or terror. People that have tried ayahuasca have said they spoke with god-like entities, elves, and extra-terrestrials. dmt tripSome would describe it as much more powerful than LSD or mushrooms. Some people will feel as though they have died and entered the god’s realm. The high is difficult to explain but whatever you feel, it’s as though it has really happened. Reality changes and with that, you experience a change in perception afterward. Some said that it felt like forced lucid dreaming or an out-of-body experience.

DMT and Ritualistic Healing
The main use for DMT is for ritualistic healing. This can be dated back to the 16th century in South America. In the 1950s, there was hope that ayahuasca could be the cure for opiate addiction. Sadly, the 1970’s drug act making psychedelics illegal in the U.S. stopped further funding on studies. Only recently has the western world started to develop new religious groups that are using ayahuasca as a means for healing. dmt ritualistic healingThey are connecting with Shamans from the Amazon rainforest in healing retreats. These retreats are said to cure mental and physical illness by giving people the ability to let go of past pains. It’s the neurotransmitter and tryptamine molecule in DMT that is responsible for the mind expansion. It is said to help users gain enlightenment, heal, and come up with new innovations. DMT can be smoked, snorted, or taken orally.

How DMT Affects the Brain
DMT with the MAO-inhibitors is an agonist on serotonin receptors in the brain. The chemical root structure in DMT is close to an anti-migraine drug. When you take DMT, it binds to your serotonin receptors. This causes neurons to react as though serotonin has been released when there is no serotonin present. This is what causes the hallucinations and separation from reality. The ritual of healing by use of DMT is being questioned by the medical field. Some believe it can help people with addiction and mental disorders.

DMT for Therapy
Research through observation has suggested that ayahuasca can have positive effects on treating drug or alcohol abuse. Ayahuasca has long been used to treat serious conditions like psychological issues, mental disorders, and addiction. Sometimes, during a trip, ayahuasca can promote the user to look at their life and see it in an alternate way. This can help them in healing any core emotional problems. It has been reported to help ease depression and anxiety. Those who have taken the drug stated that life became more manageable and they have greater control over their emotions. The therapeutic effects that people talk about regarding DMT are the mindfulness they have achieved. The way your brain works during the trip is said to bring you to a place of acceptance. By facing any past pain, users said they became more centered. Advocates believe that for these reasons, it could be a method for stopping substance abuse. This is still just a theory as no tests have proven this to be true.

Risks of DMT with Previous Conditions
While some people have reported that DMT is a healing tool, it may put certain people at risk. Most users are already used to taking psychedelic drugs and have a spiritual background. While spiritual insight is a common occurrence, some people with certain conditions will experience a negative trip. This is especially true for anyone with a pre-existing psychological problem. Someone with schizophrenia, psychosis, anxiety, or clinical depression should not take DMT. The bad trip can cause problems past the initial high, worsening conditions. dmt riskIf someone has a pre-existing heart condition, a DMT trip could cause heart failure. There are also a variety of drugs that can cause nerve damage, coma, or death when mixed with DMT. These include opioids painkillers and antidepressants.

DMT is Not FDA Approved
Since the 1970s, DMT has been illegal. This means that users will often get the drug through the internet. Using the drug without the proper guidance can prove to be dangerous. If you’re not in a controlled setting and you lose all control, you could harm yourself in the middle of the trip. You also have to use the right amount of ingredients or you risk death. While it has been deemed safe by the religious groups that use it, there’s nothing to govern users from taking it by themselves. Regardless of the theory that it’s helpful for problems like recovery from addiction, it is still illegal and not enough is known about DMT. The limited research makes it difficult to determine if it can cause dependence or addiction.

The Risk of Taking DMT
When someone takes a DMT dose that is too high, it can cause dangerous side effects. This includes seizures, heart attacks, or a coma. It isn‘t quite known if DMT is toxic to the human body. It has been found that death connected to DMT is usually due to an existing health condition or mixing DMT with other drugs. If you don’t have a guide who remains conscious, you could potentially die by asphyxiation. DMT can cause vomiting which can be lethal when you’re unconscious during a trip. This is also part of the reason shamans insist you don’t eat for a day before. When you’re outside of the ritual environment, this is where you have greater risk. Again, research is limited when it comes to DMT so far. Science hasn’t found an indication of physical dependence or addiction on the drug. It has been found that recreational users might develop a psychological craving for the drug. Using it as a type of therapy can create the user to rely on it in a way that others rely on seeing a therapist.

Side Effects of DMT
During a DMT trip, people will experience hallucinations that are more intense than any other psychedelic drug. This can expand awareness when the person is open to the extreme alternate world they become a part of. One of the worst side effects during the trip is that a person can become terrified. There is no way to get someone out of a bad trip so they must ride it out. The trip of DMT can come with powerful messages, good or bad. It might not be easy to integrate their experience into real life afterward. dmt side effectsThe side effects of DMT are lower than other hallucinogens but it’s still possible that you might experience the following:

Increase in blood pressure or heart rate
Chest may tighten
The user can become agitated
Rapid eye movement
Dizziness may occur
Vomiting
Nausea
MAOI Overdose Risks
MAO-inhibitors are what allows DMT to release its active compounds that create the high. MAOI can release poisons from many natural ingredients which can cause a dangerous rise in blood pressure. It negatively influences amphetamines, anesthetics, sedatives, antihistamines, alcohol, and antidepressant agents. Shamans are aware of the dangers of MAIO and are careful with the doses they add when creating an ayahuasca brew. An overdose of MAIO is possible with side effects such as hyperreflexia or convulsions. Even within the Supreme Court of the U.S., they are allowing the Beneficent Spiritist Center União do Vegetal to continue using ayahuasca in their spiritual practices. It seems that there is little proof found that DMT is dangerous when taken maturely and responsibly. The problems seem to arise when people abuse the drug. When a trip isn’t guided by an experienced spiritual representative, higher doses cause greater risks. Mixing DMT with other drugs or alcohol can also be dangerous. When the rituals take place, there are many precautions that taken to ensure spiritual support and safety. Recreational use is more likely to cause overdose, terrifying trips, death by asphyxiation, heart problems, and possibly further psychosis. Some have found benefits of taking DMT for their chronic emotional problems. This doesn’t take away from the fact that it’s a potent psychedelic that alters the mind.

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