Have you heard about the movement to decriminalize psychedelics, also known as entheogenic plants? With the help of a grassroots organization called Decriminalize Nature, Denver, Colorado, and Oakland and Santa Cruz in California have all decriminalized entheogenic plants to various degrees, and it’s not just because people are interested in tripping balls—the therapeutic potentials of entheogenic plants are immense. 

In addition to showing promise in helping with chronic pain, psychedelics may help many mental health conditions, including substance dependency, PTSD, depression, anxiety, and OCD. 

And this help can be lasting, with one study reporting them to have “positive long-term mental health consequences, rather than daily neurochemical corrections in brain dysfunctions,” meaning they may help treat conditions better than pharmaceuticals. 

They can work quickly, too. The same study also found that psilocybin and LSD only took two administrations, while ibogaine—from iboga, a West African shrub—showed promise in being effective in just a single administration. In a country where 1 in 5 of us need treatment for a mental health issue, the potential for healing is profound. 

Below are some therapeutic potentials of psychedelics and the conditions they may be able to help treat

Substance dependency

It’s a beautiful irony that plants lumped into the dangerous drugs pile are now being used to curtail addiction to substances, and entheogens join cannabis in this exciting therapeutic approach. 

This research article about LSD, peyote, ibogaine, and ayahuasca says their effectiveness is due to their interaction with neurotransmitter pathways strongly linked to addiction and reward, saying, “These substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable ‘after-glow’ effect that in part reflects their action on the serotonin neurotransmitter system.”

It goes on to say that “Serotonin has been long recognized as central to the psychedelics’ well-known phenomenological, physical, emotional and cognitive dynamics.” Because depressed serotonin levels tend to be found in addict populations, these serotonin-based dynamics can be very helpful in aiding substance cessation.

PTSD

Post-traumatic stress disorder is a condition that causes symptoms like trauma flashbacks and panic attacks, not uncommonly to the point where people have problems living a regular life. Because the process of psychotherapy can trigger PTSD symptoms, a new approach to treatment is warranted.

Though it’s yet to be included in the passed legislation to decriminalize psychedelics, MDMA (3,4-methylenedioxymethamphetamine) has shown a lot of promise in aiding relief from symptoms of PTSD. 

This review article from 2016 looks at several studies, concluding that “MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative effect that usually accompanies such memories.” And, it only took 2-3 sessions when combined with psychotherapy, according to the article.

Depression and anxiety

Depression and anxiety affect millions of people in the US. As this review article points out, psilocybin and MDMA can result in “substantial and sustained improvement among people with treatment-resistant depression and anxiety.” 

The article notes that this idea is nothing new, and “During the 1950s and early 1960s, research sponsored by the National Institute of Mental Health demonstrated potential for drugs of this class to markedly alleviate depression and existential suffering among people with cancer.

The article goes on to say that psilocybin and LSD provide a “reframing of experience and relationship to others and the world,” and the results of safely administered psychedelics tended to be, “a state of wonder, conceptual frame shift, expanded capacity for love, and an intensified sense of connection. Patients living with medical conditions that had robbed them of hope or reason to live may experience a transformative shift in perspective and experience of inherent meaning, value, and worth.”

OCD

Obsessive compulsive disorder is characterized by obsessive thoughts and fears that lead to compulsive behaviors. It’s commonly complicated by issues like delusions, suicidal thoughts, and panic, among others. 

This study found clinically administered psilocybin to be associated with “symptomatic reduction of OCD symptoms in subjects with treatment-resistant OCD.” 

The study also found, incidentally (and interestingly), that “5 [out of 9] of the subjects readily described their experiences as very psychologically and spiritually enriching. Four subjects reported during HD [high dose] profound positive transcendental experiences such as exploration of other planets, visiting past life reincarnations, and interacting with deities.” (Hey, bonus.)

Chronic pain

Studies on chronic pain generally aren’t impressive, but anecdotal evidence that psychedelics can help ease chronic pain is abundant, especially when microdosing—so much so that researchers conducted this study on the self-reported benefits of microdosing. It states that “The current survey demonstrates that self-medication with MDP [microdosed psychedelics] was experienced to be more effective compared to conventional treatment in case of anxiety, ADHD/ADD, and physiological disorders such as pain.” 

And changa—a blend that includes DMT-infused materials and ayahuasca plant—was found to be promising in this study, which focuses on the analgesic (pain-killing) effects: “The case reported here suggests that changa can produce a long-lasting analgesic effect, involving a combination of mood-enhancing effects; other psychological factors; an interaction with several neurotransmitter systems; and anti-inflammatory, neuroprotective, and plasticity-promoting actions. Remarkably, changa could offer pain treatment that targets multiple monoamine neurotransmitters.”RelatedHow cannabis relieves different types of pain

As with cannabis, there’s much research to be done on these exciting potential modes of natural healing. Hopefully the movement to decriminalize will help solidify this work in coming years—helping to, quite literally, stop the madness. (If you’re interested in getting decriminalization rolling in your community, reach out to Decriminalize Nature.)

In conclusion, we’ll end with an inspiring quote from this 2018 study: “If neglect, trauma, childhood adversities, poverty, abuse, and deprivation—i.e., mental injuries—can have lasting negative consequences for mental health, it is also logically plausible that positive, cathartic experiences, sometimes of the mystical type, reliably achieved in PAP [psychedelic-assisted-psychotherapy], can induce long lasting positive mental health outcomes.”

Healing With the Psychonauts: Psychedelic Medicine Goes Mainstream

(Gillian Levine for M&H Research Chemicals)Plant medicines and psychedelic healing are getting serious attention from many quarters of the mainstream these days.

Michael Pollan’s book How to Change Your Mind has been on the New York Times bestseller list for nine weeks.

Ayelet Waldman is microdosing and having A Really Good Day, and rom-com audiences have been subjected to Ben Stiller’s laughable-yet-so-not-funny ayahuasca trip in While We’re Young.The Los Angeles Psychedelic Science Symposium aimed to make LA the center of the new psychedelic medicine awakening.

More significantly, next month, the American Psychological Association will host a panel on “Psychedelics and Psychology” at its annual convention, the first of its kind in the organization’s history. Tripping balls is becoming legit.

A smorgasbord of doctors, shamans, veterans, academics, psychonauts, and therapists gathered last month at UCLA to talk about psychedelic drugs and their potential to save humanity from itself.

This was the Los Angeles Psychedelic Science Symposium (LAPSS), the first conference of its kind to be held in a major Los Angeles academic institution. Its mission: to make Los Angeles a hub of psychedelic information and research, and spread the word about the healing powers of psychedelics.

To that end, the event brought together rock stars of the entheogenic world, including Dennis McKenna, James Fadiman, Gabor Maté, and James Oroc, with lesser-known researchers, therapists, and everyday people whose lives have been saved by Schedule 1 drugs.  The goal of the Los Angeles Psychedelic Science Symposium, according to event coordinator Wallis Back, was to provide opportunities for the world’s leading experts in the field of psychedelic science to educate a diverse audience with current evidence-based research, in addition to medicinal and therapeutic applications.

How Tim Leary Derailed Clinical Use

Poison Control reports that the number of calls to poison control centers in California involving cannabis ingestion in people 19 and younger rose from 347 in 2015 to 588 in 2017, when it became legal for adults to possess pot. About half of those involved kids ages five and under.

The history of psychedelics in America is complicated, but essentially has two arcs. The first began in the 1950s, with the flowering of psychedelic research and cultural acceptance.  Major LSD studies were conducted at Harvard and Stanford, more than a thousand research papers were published, international conferences seriously discussed the clinical use of psychedelic drugs. CBS even ran a glowing special report on the promise of LSD. But then Timothy Leary, the Harvard-researcher-turned-counterculture-clown, started flinging tabs of acid around like rice at a wedding and ruined it for everyone.

Canadian physician and author Gabor Maté, addressing the LAPSS conference last month, likened Leary and his hippie brethren of the ‘60s to Mickey Mouse in The Sorcerer’s Apprentice. “The sorcerer used potions and incantations to do good,” Maté said, “but he knew how to control those forces, he knew how to marshal them in the service of positive outcomes. In his absence, Mickey, without his training, without the expertise or wisdom, starts releasing these forces and they wreak all kinds of havoc, because it’s not the right context. In the ‘60s a lot of people started using psychedelics like Mickey Mouse.”

Some people had bad trips and got hurt. President Nixon declared Timothy Leary “the most dangerous man in America.” By 1970, psychedelics had been categorized as Schedule 1 drugs (determined to have no accepted medical use and a high potential for abuse) by the DEA, and federal funding for research was withdrawn. Scientists who were just figuring out how powerful and useful psychedelics really were had to either give up their research or do it in secret.

Gabor Maté: Inside the Psychedelic Experience

The Underground Era

Psychedelics went underground but did not go away. In the meantime, other parts of the landscape shifted: Globalism and the internet brought indigenous plant medicines like ayuhuasca, iboga, peyote and DMT to Western attention. Those drugs have been percolating through American psychedelic culture for about a decade, creating converts in their wake.Psychedelics have extraordinary efficacy in treating the illnesses that currently plague America: trauma, addiction, depression, anxiety.

Perhaps most significantly, the conversation about medicinal psychedelics is now taking place because a space has been opened for it through the mainstream acceptance of cannabis as a legal and legitimate medicine.

Forty years after going underground, the conversation around psychedelics is coming back into the open. Organizations like the Los Angeles Medicinal Plant Society (LAMPS), and the Multidisciplinary Association for Psychedelic Studies (MAPS), which co-hosted the Los Angeles conference, kept the lights on through the long, psychedelic dark age—and now are helping bring research and knowledge to thousands of interested clinicians and patients.

The LAPSS is one of many such conferences that have taken place in 2018 alone. As the LAPSS was taking place in Los Angeles, a similar conference was unfolding in Prague. A recent article on the American Psychological Association’s website states that “research studies have continued to point to the possibility that the benefits of these illegal drugs may outweigh the risks in certain scenarios.”

America in a Time of Need

All of this comes not a moment too soon. Studies show that psychedelics have extraordinary efficacy in treating the illnesses that currently plague America: trauma, addiction, depression, anxiety, isolation, disaffection, and crippling fear of death.Psychedelics both attract and create people who are rule-breakers, folks given to wearing hemp clothing and face studs.

Anthony Bossis, a doctor who has overseen psilocybin trials with terminal cancer patients at NYU, reported that subjects in his study all experienced significant relief from depression and lessened anxiety about death. Patients in Bosses’s care were able to transcend their fear of mortality, increase their sense of purpose, and deepen their connections with friends and loved ones, he said.

He offered the LAPSS audience a flurry of graphs and brain scan graphics to prove his point, but he was preaching to the converted. At one point someone asked the audience for a show of hands of those who had tried a hallucinogen. Too many hands went up to count, so the question was rephrased: Who in the audience hadn’t taken entheogens? In a room of close to 500 souls, fewer than 20 hands went into the air.

Serious Talks, Moving Moments

The LAPSS tone was decidedly non-Mickey Mouse.  The conference offered serious talks on everything from MDMA-assisted psychotherapy for PTSD, to psychedelics and autoimmune conditions, to a panel called “The Moderating Effect of Psychedelics on the Prospective Relationship Between Prescription Opioid Use and Suicidality Among Marginalized Women.” We’ve come a long way from the Merry Pranksters.

A particularly moving moment came during a panel called “Veterans Helped by the Medicine.” Mathew Kahl, a veteran of the Iraq war, came home wracked with injuries and dependent on 20 different pharmaceuticals: “opioids and benzos together; large quantities, it was obscene.” He described how he used cannabis at first to wean himself off the pharmaceuticals, then ayuhuasca to transform his pain and his own identity. “I’m no longer a soldier, I’m not just an infantryman,” Kahl said. “I’m not just a man, I’m a human being. It has taught me how to be a human being again.”

A Transitional Conference

For all its seriousness, there was also a festive, slightly renegade feeling to the weekend. Psychedelics both attract and create people who are rule-breakers, folks given to wearing hemp clothing  and face studs. They sport cryptic tattoos, fall into spontaneous group hugs, and vape like mad on lunch breaks.

The culture of the Los Angeles Psychedelic Science Symposium illustrated where the world of psychedelics finds itself in this transitional moment. Proponents are trying to bring legitimacy to a movement that got hijacked long ago by hippies, without alienating the hippies themselves. Fortunately, psychonauts have no trouble reconciling the different narratives; actually, they don’t worry about it. Everyone is welcome in an eclectic ecosystem still seeking its contemporary identity.

As a steady roll of speakers held the stage, the back of UCLA’s Ackerman Ballroom was set up like a psychedelic science fair, with exhibitors displaying densely-worded, slightly inscrutable posters for psycho-chemical phenomena that would require the skills of a PhD to decipher. There were pamphlets and swag for everything from psilocybin-assisted retreats to post-journey integration services. There was even a giant, papier maché magic mushroom.

This is the world of psychedelics as we find it today, a wacky place where academics hobnob with sound healers. The marketplace of ideas surrounding psychedelics is similar to that of cannabis before it went legal and pro: It’s still championed by the fringe, but any entrepreneur with an ounce of vision can see its staggering commercial potential.

Chilling in the Psychic Lounge

Psychonauts are a groovy, mellow bunch, and the organizers of the Los Angeles Psychedelic Science Symposium considerately offered patrons a space to chill. Down the hall was a “Psychic Lounge,” where tired psychonauts could take a timeout and shop for books, network, get chair massages, and listen to “shamanic sound journeys.”Even in our legal age, healing thyself still may involve committing a federal crime.

Crystal bowls sang and sound baths were taken. Wandering around the LAPSS rewarded the casual eavesdropper with gems like: “After iboga, I could talk to plants. I could walk up to a tree and introduce myself and it would start talking to me.” In a stall in the ladies’ room somebody had scrawled, “You are yesterday.”

By the close of the event we were all ready to go out and start microdosing. But therein lies the problem that surrounds all of this inspiring information. Psychedelics are still illegal, and the pathway to legality—or even ways to make these drugs more open to university researchers—appears long. There’s growing support among a number of communities for more research into psychedelics, but the drugs themselves are difficult for scientists to obtain. Healing thyself still means heading down a back alley to commit a federal crime. Whether the combined efforts of academic researchers and impassioned psychonauts will help ease restrictions was a widely shared concern at LAPPS—and one that may be years from resolution.

1P LSD first debuted online as a research chemical in 2015. It has been sold as a designer psychedelic drug ever since. Little is known about its invention as academic literature about the substance does not exist prior to its debut online. Due to the lack of analytical, chemical, and pharmacological data on 1P LSD. Conclusive scientific evidence is lacking on its properties, behavior, and risks. However, it is assumed that it functions similarly to LSD. According to user accounts, its subjective effects are almost identical. 

It is considered an analogue to LSD.  An analogue is a substance that is structurally and functionally similar to the original substance. It was created by modifying the molecular structure of LSD, probably in an attempt to produce a novel derivative of LSD that would technically fall into a legal loophole in many countries. it is also a homologue of ALD-52, which means that a molecular chain was added to its parent molecule.

The United States does not control it on the federal level. However, it could be considered an analogue, which would make it illegal under the Federal Analogue Act.

What You Will Learn About 1P LSD

  • It is a psychedelic substance of the lysergamide class and is considered an analogue of LSD and homologue of ALD-52. It also could be a “prodrug” of LSD. 
  • The legality of 1P LSD varies from country to country. However, it is illegal in 13 countries.
  • Because it is so closely related to LSD, it is considered relatively safe to use. However, there are increased risks if you have a pre-existing medical condition, heart condition, or are on certain kinds of medications.
  • 1P LSD first appeared online in 2015 as a designer drug. We don’t know who first created it, although some speculate that it was Alexander Shulgin.

What is 1P LSD? 

It is short for 1-propionyl-lysergic acid diethylamide. As an analogue of LSD and homologue of ALD-52, it is classified as a psychedelic substance of the lysergamide class. 1P LSD is made by adding a propionyl group to the nitrogen molecule of LSD’s indole. In other words, it is the same substance as LSD with an additional chemical chain. Recently, it has become available as a research chemical in the form of blotters and powdered material. Typically, it takes 45-90 minutes to begin to feel the effects and lasts anywhere between 8-12 hours,

Pharmacology

Though it functions similarly to LSD, too little research exists to make definitive claims. However, due to its chemical similarities, it functions as a serotonergic substance. It binds to the 5-HT serotonin receptors in the brain or body. The way LSD binds to the 5-HT2A receptor, in particular, causes a cross-activation of the 5-HT2A receptor heteromer. In other words, this relationship produces long-lasting psychedelic effects. 1P-LSD probably binds with the monoamine receptors responsible for dopamine and norepinephrine but, again, little data exists to back up these claims.  

A study from 2015 indicated that it shows 38% the potency of LSD in mice, though the drug did exhibit LSD-like behavior. There is a theory that 1P-LSD may act as a prodrug for LSD, which would mean that it turns into LSD once metabolized in the body. However, more studies need to be conducted in order to determine how 1P-LSD functions and if it is capable of producing its own psychedelic effects.

1P LSD & LSD: What’s the Difference?

Subjectively speaking, users claim that the effects are more or less identical. However, a recent study investigated the similarities and differences in mice. Researchers found that 1P LSD shows 38% of the potency of LSD. This could indicate that 1P LSD is a prodrug, which means that it metabolizes into LSD in the body. The process could make it weaker in comparison as well as slower to take effect. According to users, however, this does not seem to accurately reflect their experiences,1p lsd for sale . 

The main differences include:

  • Molecular weight: LSD, 320g/mol | 1P LSD, 380g/mol.
  • 1P LSD: has three more carbons and one more oxygen in its molecular structure than LSD has. 
  • Legalities: LSD is an illegal drug in most countries. 1P LSD is a research chemical and is legal.
  • Effects: 1P LSD may be more stimulating and fast-paced in regard to its physical and cognitive effects. However, overall, the average user expresses that they cannot tell the difference.

Benefits & Risks

Concerning the risks and benefits of 1P LSD, know how much you’re taking and what kind of experience you are looking for. If you’re new to psychedelics, doing it alone might not be advisable. An unfavorable set and setting could potentiate a series of issues. 

If you’re taking medications or have a pre-existing condition, particularly those defined as cardiovascular or mental, then consult a trained physician or expert before taking any substance. There is a risk of vasoconstriction in the heart, and psychosis for bipolar disorder and schizophrenia,1p lsd for sale. Furthermore, mixing certain pharmaceutical drugs may counter-interact with 1P LSD as well. Benzodiazepine tends to lower the effectiveness of lysergic acid diethylamide and any other psychedelic substance. Mixing certain antidepressants with LSD can result in serotonin syndrome due to an overload of serotonin in the central nervous system. 

Other concerns include HPPD and PTSD. HPPD, or hallucinogen persisting perception disorder, is a disorder where users see “visual snow” long after the trip has ended. This can disrupt an individual’s ability to perform regular tasks due to the distraction caused by visual snow. In more extreme cases HPPD can result in severe hallucinations for prolonged periods of time.

All these factors indicate the need for preparation and forethought to reduce the risks of taking 1P LSD.

Aside from that, the risks of 1P LSD are technically unknown. Since science governs the area of medicine, when we speak about a substance we cannot make definite claims about them unless backed up by science. Personal accounts, even if there are thousands, cannot technically be credited as factual.  However, 1P LSD appears to function like LSD, which would make it a relatively low-risk drug since scientific evidence on LSD shows that there are minimal adverse effects.

Top Reported Benefits

Recently, a resurged interest in LSD has led scientists to reconsider the studies that were conducted in the 50s and 60s. Those investigations primarily focused on treating depression, post-traumatic stress disorder, drug dependency, and reducing anxiety in end-of-life patients. Since the effects are similar to LSD, it might be able to address these issues and their associated symptoms.

The top reported benefits include:

  • Dissolution of the ego.
  • A decrease in anxiety and depression.
  • Euphoria.
  • Spiritual enhancement and feelings of unity.

What to know about ketamine .

Ketamine: Also called “Special K,” this animal tranquilizer is sometimes used as a recreational drug by attendees at dance raves and other events. The drug may also effectively combat the symptoms of depression.What to know about ketamine .

A 2012 study from the journal Science found that ketamine may help stimulate the growth of synapses in the brain, and beneficial effects of the drug on people with chronic depression can occur within hours. “The rapid therapeutic response of special K in treatment-resistant patients is the biggest breakthrough in depression research in a half century,” Ronald Duman, professor of psychiatry and neurobiology at Yale University, said in a statement.

Ketamine is a medication mainly used for starting and maintaining anesthesia. It induces a trance-like state while providing pain reliefsedation, and memory loss. Other uses include for chronic pain, sedation in intensive care, and depression. Heart function, breathing, and airway reflexes generally remain functional. Effects typically begin within five minutes when given by injection, and last up to about 25 minutes.

Common side effects include agitation, confusion, or hallucinations as the medication wears off. Elevated blood pressure and muscle tremors are relatively common.Spasms of the larynx may rarely occur. Ketamine is an NMDA receptor antagonist, but it may also have other actions.

Ketamine was discovered in 1962, first tested in humans in 1964, and was approved for use in the United States in 1970.It was extensively used for surgical anesthesia in the Vietnam War due to its safety. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale price in the developing world is between US$0.84 and US$3.22 per vial. Ketamine is also used as a recreational drug for its hallucinogenic and dissociative effects.

Medical uses What to know about ketamine .

Anesthesia

Uses as an anesthetic:

Anesthesia in children, as the sole anesthetic for minor procedures or as an induction agent followed by muscle relaxant and tracheal intubation

Asthmatics or people with chronic obstructive airway disease

As a sedative for physically painful procedures in emergency departments

Emergency surgery in field conditions in war zones

To supplement spinal or epidural anesthesia/analgesia using low doses

Since it suppresses breathing much less than most other available anesthetics, ketamine is used in medicine as an anesthetic; however, due to the hallucinations it may cause, it is not typically used as a primary anesthetic, although it is the anesthetic of choice when reliable ventilation equipment is not available.What to know about ketamine .

Ketamine is frequently used in severely injured people and appears to be safe in this group. A 2011 clinical practice guideline supports the use of ketamine as a dissociative sedative in emergency medicine.  It is the drug of choice for people in traumatic shock who are at risk of hypotension. low blood pressure is harmful in people with severe head injury and ketamine is least likely to cause low blood pressure, often even able to prevent it.

The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics. When used at anesthetic doses, it will usually stimulate rather than depress the circulatory system. It is sometimes possible to perform ketamine anesthesia without protective measures to the airways. Ketamine is considered relatively safe because protective airway reflexes are preserved.

Ketamine is used as a bronchodilator in the treatment of severe asthma.However, evidence of clinical benefit is limited.What to know about ketamine .

Pain management what to know about ketamine .

Ketamine may be used for postoperative pain management. Low doses of ketamine may reduce morphine use, nausea, and vomiting after surgery.

Ketamine has similar efficacy to opioids in a hospital emergency department setting for management of acute pain and for control of procedural pain.

It may also be used as an intravenous analgesic with opiates to manage otherwise intractable pain, particularly if this pain is neuropathic. It has the added benefit of counteracting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines. Ketamine is an analgesic that is most effective when used alongside a low-dose opioid; because, while it does have analgesic effects by itself, the doses required for adequate pain relief when it is used as the sole analgesic agent are considerably higher and far more likely to produce disorienting side effects. A review article in 2013 concluded, “despite limitations in the breadth and depth of data available, there is evidence that ketamine may be a viable option for treatment-refractory cancer pain”.

Low-dose ketamine is sometimes used in the treatment of complex regional pain syndrome (CRPS). A 2013 systematic review found only low-quality evidence to support the use of ketamine for CRPS.

Depression

Ketamine has been found to be a rapid-acting antidepressant in depression. It also may be effective in decreasing suicidal ideation, although based on lower quality evidence. The antidepressant effects of ketamine were first shown in small studies in 2000 and 2006. They have since been demonstrated and characterized in subsequent studies. A single low, sub-anesthetic dose of ketamine given via intravenous infusion may produce antidepressant effects within four hours in people with depression. These antidepressant effects may persist for up to several weeks following a single infusion. This is in contrast to conventional antidepressants like selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), which generally require at least several weeks for their benefits to occur and become maximal. Moreover, based on the available preliminary evidence, the magnitude of the antidepressant effects of ketamine appears to be more than double that of conventional antidepressants. On the basis of these findings, a 2017 review described ketamine as the single most important advance in the treatment of depression in over 50 years. It has sparked interest in NMDA receptor antagonists for depression, and has shifted the direction of antidepressant research and development.What to know about ketamine .

Ketamine has not been approved for use as an antidepressant, but its active enantiomeresketamine, has been. Esketamine was developed as a nasal spray for treatment-resistant depression and is approved for use in the United States. While there is evidence to support the effectiveness of ketamine in treating depression, there is a lack of consensus on optimal dosing and the effects and safety of long-term therapy.  Ketamine can produce euphoria and dissociative hallucinogen effects at higher doses, and thus has an abuse potential.  Moreover, ketamine has been associated with cognitive deficitsurotoxicityhepatotoxicity, and other complications in some individuals with long-term use. These undesirable effects may serve to limit the use of ketamine for depression.  Dozens of “ketamine clinics” have opened across the United States, where intravenous ketamine is used off-label to treat people with depression. What to know about ketamine .

Contraindications

The use of ketamine is cautioned against in cases of:

Conditions worsened by an increase in blood pressure or heart rate, such as anginastroke, poorly controlled high blood pressure. Ketamine increases both heart rate and blood pressure.

Psychiatric disorders: Ketamine can cause hallucinations, and therefore may exacerbate the symptoms of certain psychiatric disorders.

Ketamine was once thought to cause increased intracranial pressure (IICP): as of 2014, this is believed not to be the case.

Raised intraocular pressure (IOP): Ketamine can further increase IOP.

Penetrating eye injury: Can increase risk of loss of eye contents, due to increased IOP.

Acute porphyria: Ketamine is considered porphyrinogenic, that is, it may provoke an attack of acute porphyria, a disease of the nervous system, in susceptible people.

Side effects What to know about ketamine .

When administered by trained medical professionals, ketamine is generally safe for those people who are critically ill. Even in these cases, there are known side effects that include one or more of the following:

Cardiovascular: abnormal heart rhythmsslow heart rate or fast heart ratehigh blood pressure or low blood pressure

Central nervous system: Ketamine is traditionally avoided in people with or at risk of intracranial hypertension (ICP) due to concerns about ketamine causing increased intracranial pressure. It does not increase ICP more than opioids.

Dermatologic: Transient reddening of the skin, transient measles-like rash

Gastrointestinal: reduced appetite, nausea, increased salivation, vomiting

Local: Pain, eruptions or rashes at the injection site

Neuromuscular and skeletal: Increased skeletal muscle tone (tonic-clonic movements)

Ocular: Double vision, increased intraocular pressureinvoluntary eye movementstunnel vision

Respiratory: Airway obstruction, cessation of breathing, increased bronchial secretions, reduced effort to breathe, spasm of the vocal cords (larynx)

Other: Anaphylaxis, dependence, emergence reaction

At anesthetic doses, 10–20% of people experience adverse reactions that occur during emergence from anesthesia, reactions that can manifest as seriously as hallucinations and delirium. These reactions may be less common in some subpopulations, and when administered intramuscularly, and can occur up to 24 hours postoperatively; the chance of this occurring can be reduced by minimizing stimulation to the person during recovery and pretreating with a benzodiazepine, alongside a lower dose of ketamine. People who experience severe reactions may require treatment with a small dose of a short- or ultrashort-acting barbiturate.

Tonicclonic movements are reported at higher anesthetic doses in greater than 10% of people.

Neurological

Effects of ketamine on Zebrafish development. Green areas indicate neurons, and increasing doses of ketamine reduced growth of neurons from the spinal cord.

In 1989, psychiatry professor John Olney reported ketamine caused irreversible changes, known as Olney’s lesions, in two small areas of the rat brain. However, the rat brain has significant differences in metabolism from the human brain; therefore such changes may not occur in humans.

The first large-scale, longitudinal study of ketamine users found current frequent (averaging 20 days/month) ketamine users had increased depression and impaired memory by several measures, including verbal, short-term memory, and visual memory. Current infrequent (averaging 3.25 days/month) ketamine users and former ketamine users were not found to differ from controls in memory, attention, and psychological well-being tests. This suggests the infrequent use of ketamine does not cause cognitive deficits, and that any deficits that might occur may be reversible when ketamine use is discontinued. However, abstinent, frequent, and infrequent users all scored higher than controls on a test of delusional symptoms.

Short-term exposure of cultures of GABAergic neurons to ketamine at high concentrations led to a significant loss of differentiated cells in one study, and noncell-death-inducing concentrations of ketamine (10 μg/ml) may still initiate long-term alterations of dendritic arbor in differentiated neurons. The same study also demonstrated chronic (>24 h) administration of ketamine at concentrations as low as 0.01 μg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal maintenance and development.

More recent studies of ketamine-induced neurotoxicity have focused on primates in an attempt to use a more accurate model than rodents. One such study administered daily ketamine doses consistent with typical recreational doses (1 mg/kg IV) to adolescent cynomolgus monkeys for varying periods of time. Decreased locomotor activity and indicators of increased cell death in the prefrontal cortex were detected in monkeys given daily injections for six months, but not those given daily injections for one month. A study conducted on rhesus monkeys found a 24-hour intravenous infusion of ketamine caused signs of brain damage in five-day-old but not 35-day-old animals.

Some neonatal experts do not recommend the use of ketamine as an anesthetic agent in human neonates because of the potential adverse effects it may have on the developing brain. These neurodegenerative changes in early development have been seen with other drugs that share the same mechanism of action of NMDA receptor antagonism as ketamine.

The acute effects of ketamine cause cognitive impairment, including reductions in vigilance, verbal fluency, short-term memory, and executive function, as well as schizophrenia-like perceptual changes.

Urinary tract

A 2011 systematic review examined 110 reports of irritative urinary tract symptoms from ketamine recreational use. Urinary tract symptoms have been collectively referred as “ketamine-induced ulcerative cystitis” or “ketamine-induced vesicopathy”, and they include urge incontinence, decreased bladder compliance, decreased bladder volume, detrusor overactivity, and painful blood in urineBilateral hydronephrosis and renal papillary necrosis have also been reported in some cases. The pathogenesis of papillary necrosis has been investigated in mice, and mononuclear inflammatory infiltration in the renal papilla resulting from ketamine dependence has been suggested as a possible mechanism.What to know about ketamine .

The time of onset of lower urinary tract symptoms varies depending, in part, on the severity and chronicity of ketamine use; however, it is unclear whether the severity and chronicity of ketamine use correspond linearly to the presentation of these symptoms. All reported cases where the user consumed greater than 5 g/day reported symptoms of the lower urinary tract. Urinary tract symptoms appear to be most common in daily ketamine users who have used the drug recreationally for an extended period of time. These symptoms have presented in only one case of medical use of ketamine. However, following dose reduction, the symptoms remitted.

Management of these symptoms primarily involves ketamine cessation, for which compliance is low. Other treatments have been used, including antibioticsNSAIDssteroidsanticholinergics, and cystodistension. Both hyaluronic acid instillation and combined pentosan polysulfate and ketamine cessation have been shown to provide relief in some people, but in the latter case, it is unclear whether relief resulted from ketamine cessation, administration of pentosan polysulfate, or both. Further follow-up is required to fully assess the efficacy of these treatments.

Liver

In case reports of three people treated with esketamine for relief of chronic pain, liver enzyme abnormalities occurred following repeat treatment with ketamine infusions, with the liver enzyme values returning below the upper reference limit of normal range on cessation of the drug. The result suggests liver enzymes must be monitored during such treatment.

Dependence

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Radar plot showing relative physical harm, social harm, and dependence of ketamine

Ketamine’s potential for dependence has been established in various operant conditioning paradigms, including conditioned place preference and self-administration; further, rats demonstrate locomotor sensitization following repeated exposure to ketamine.[75] Increased subjective feelings of ‘high’ have been observed in healthy human volunteers exposed to ketamine. Additionally, the rapid onset of effects following smoking, insufflation, and/or intramuscular injection is thought to increase the drug’s recreational use potential. The short duration of effects promotes bingeingtolerance can develop; and withdrawal symptoms, including anxiety, shaking, and palpitations, may be present in some daily users following cessation of use.What to know about ketamine .

Ketamine can cause a variety of urinary tract problems that are more likely to occur with heavier and/or higher dosed use, especially in those not watching for a healthy lifestyle, according to a UK study.