Marijuana Compound Treats Schizophrenia with Few Side Effects: Clinical Trial

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A compound found in marijuana can treat schizophrenia as effectively as antipsychotic medications, with far fewer side effects, according to a preliminary clinical trial.

Researchers led by Markus Leweke of the University of Cologne in Germany studied 39 people with schizophrenia who were hospitalized for a psychotic episode. Nineteen patients were treated with amisulpride, an antipsychotic medication that is not approved in the U.S., but is comparable to other medications that are.

The rest of the patients were given cannabidiol (CBD), a substance found in marijuana that is thought to be responsible for some of its mellowing or anxiety-reducing effects. Unlike the main ingredient in marijuana, THC, which can produce psychotic reactions and may worsen schizophrenia, CBD has antipsychotic effects, according to previous research in both animals and humans.

Neither the patients nor the scientists knew who was getting which drug. At the end of the four-week trial, both groups showed significant clinical improvement in their schizophrenic symptoms, and there was no difference between those getting CBD or amisulpride.

(MORE: The Complex Link Between Marijuana and Schizophrenia)

“The results were amazing,” says Daniele Piomelli, professor of pharmacology at the University of California-Irvine and a co-author of the study. “Not only was [CBD] as effective as standard antipsychotics, but it was also essentially free of the typical side effects seen with antipsychotic drugs.”

Antipsychotic medications can potentially cause devastating and sometimes permanent movement disorders; they can also reduce users’ motivation and pleasure. The new generation of antipsychotic drugs also often leads to weight gain and can increase diabetes risk. These side effects have long been known to be a major obstacle to treatment.

In the German study, published online in March by the journal Translational Psychiatry, weight gain and movement problems were seen in patients taking amisulpride, but not CBD.

“These exciting findings should stimulate a great deal of research,” says Dr. John Krystal, chair of psychiatry at Yale University School of Medicine, who was not associated with the research. He notes that CBD not only had fewer side effects, but also seemed to work better on schizophrenia’s so-called “negative symptoms,” which are notoriously hard to treat.

Negative symptoms include social withdrawal, blunting of pleasure and lack of motivation, which commonly occur in schizophrenia. Since current antipsychotic medications can themselves cause the same problems, however, it wasn’t clear whether CBD was better than amisulpride at treating these symptoms, or whether CBD simply caused fewer side effects to begin with.

(MORE: Stoned Driving Nearly Doubles the Risk of Fatal Car Crash)

Nevertheless, the new research helps elucidate the intricate complexities of the brain’s natural cannabinoid system and how CBD may work to alleviate symptoms of schizophrenia. Years ago, Piomelli and his colleagues discovered that people with schizophrenia have elevated levels of anandamide — a neurotransmitter that activates the same receptor activated by THC — in their cerebrospinal fluid, suggesting that they also had higher levels of it in the brain.

The difference was huge: anandamide levels were nine times higher in schizophrenic people than in mentally healthy controls, Piomelli says.

The researchers theorized that these radically high levels would correlate with hallucinations and delusions: the more anandamide bathing patients’ brains, the worse their disease would be. The thinking was, in essence, that people with schizophrenia are constantly high on their own natural THC.

But what the researchers actually found was the opposite. “What you get is not a positive correlation, but a negative one. The higher the levels of anandamide, the lower the symptoms,” Piomelli says.

It didn’t seem to make much sense at first, but research in both animals and humans now shows that anandamide is a natural stress reliever and antipsychotic. Piomelli thinks that the high levels seen in people with schizophrenia aren’t the cause of the problem, but the result of the brain’s attempts to solve it.

(MORE: Study: Smoking Marijuana Not Linked with Lung Damage)

The new study confirmed that as CBD relieved patients’ symptoms, anandamide levels rose in concert. “It looks like anandamide is a signaling molecule that has evolved to help us cope with stress,” Piomelli says. “In the brain, everything it does seems to be related to ways of relieving stress. It can relieve anxiety and reduce the stress response. It is involved in stress-induced analgesia [when you stop feeling pain while fighting or fleeing]. These are all mechanisms to help us prevent [negative outcomes related to stress],” says Piomelli.

“If Dr. Piomelli is right, then the brain is exquisitely sensitive to changes in anandamide levels,” says Krystal.

This raises another question, however. THC itself mimics anandamide. If high levels of anandamide are helpful for schizophrenia, why does marijuana smoking intensify psychotic states?

Here’s where it gets complex. THC mimics not only anandamide, but also another cannabinoid, 2-AG, which fits the same receptors and is far more common. “There is 200 times more 2-AG than anandamide in the brain,” Piomelli says. “At the end of the day, the complexity is such that 2-AG has a whole cluster of effects. Anandamide has completely different effects, sometimes even opposite effects. That is why with THC you get a big mess.”

(MORE: Marijuana May Both Trigger and Suppress Psychosis)

Complicating matters further, when chronic marijuana smokers build up a tolerance to THC, it may down-regulate the entire system, making it harder for anandamide to have its positive effects. This may be why some studies find that people with schizophrenia who smoke marijuana get worse.

So, where does CBD fit in? It doesn’t attach to a receptor like THC, or fool the brain into thinking that it’s getting extra anandamide or 2-AG. “What CBD seems to be doing is preventing anandamide from being destroyed,” says Piomelli. That allows the substance to exert its stress-reducing and antipsychotic effects on the brain longer, without the negative effects of THC.

If replicated, the results suggest that CBD may be at least as effective as existing drugs for the treatment of schizophrenia, without the severe side effects that make patients reluctant to take medication. The catch: “The real problem with CBD is that it’s hard to develop for a variety of silly reasons,” says Piomelli.

Because it comes from marijuana, there are obvious political issues surrounding its use. Extracting it from the plant is also expensive. But the biggest barrier may be that CBD is a natural compound, and therefore can’t be patented the way new drugs are. That means that despite the possibility that it could outsell their current blockbuster antipsychotic drugs, pharmaceutical companies aren’t likely to develop it — a particularly striking fact when you consider that every major manufacturer of new generation antipsychotics in the U.S. has so far paid out hundreds of millions or billions of dollars in fines for mismarketing these drugs. Yet they still reaped huge profits.

(MORE: The Case Against the Ban on ‘Bath Salts’ and Fake Marijuana)

Piomelli and others are working to develop synthetic versions of CBD that would avoid such hurdles. “We have one and are hoping to move forward in the near future,” he says.

For people with schizophrenia and their families, of course, it is likely to be infuriating that non-scientific issues like marijuana policy and patenting problems could stand in the way of a treatment that could potentially be so restorative. While it’s possible that these study results may not hold up or that researchers could discover problems related to long-term use of CBD,  it’s hard to imagine that they could be any worse than what patients already experience.

Maia Szalavitz is a health writer for TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland’s Facebook page and on Twitter at @TIMEHealthland.

10 comments
SteveMcCrea
SteveMcCrea

What a shame that commercial and political reasons should prevent this from being available. There ought to be some way for this to be developed through a private or government grant, and distributed through some form of licensing. Not everyone wants to make multi-billions while slowly torturing their clients to death. There would definitely be some folks who would be willing to make a low-profit, high-volume business out of this. 


Corporate capitalism is so disgusting sometimes...


---- Steve

kirklazarus19
kirklazarus19

What I've found works the best is unflowered OG Kush. Basically you grow a plant and keep in perpetual vegetative state. Just cut off some leaves hang them out to dry and then smoke them. I checked with a lab, and what I found is that using this method and this strain there is a tremendous amount of cannabinoids including thca but almost no thc. You could decarboxilate it by drying it in an oven, but then it would probably make psychotic symptoms worse, and for me just being pulled out of a psychotic state over 5 minutes is an awesome feeling. Without medication I injure myself constantly and don't realize it immediately, with using cannabis in this way there are no side effects, other than being able to feel my skin, remembering to eat, and the ability to sleep at night. It's not legal to use or grow where I live, so doing so creates an enormous risk, but so does using legally prescribed antipsychotics, anyone can order seeds online and grow their own, and any of the medical strains with high thc, are going to have high cannabinoids if they are not put into the flower stage, well og kush does I assume it would be no different with other strains. Herbies seeds is a good place to start. During the flowering stage is when the buds develop and the thca and other cannabinoids get turned into thc, which you really don't need for psychiatric symptoms. 40$ in seeds can treat you for life, I spent that much or more a week for meds that just make me physically ill and completely dysfunctional.

ionmagic
ionmagic

I am an old woman and have been a legal medical marijuana patient in Washington State for five years.  I use (and therefore, grow for myself) a specific strain of cannabis so that I can be confident it is the "correct" and specific strain i need, and that it has been properly processed. I have a job, i own my home, i pay taxes, and i vote.

My beloved husband is NOT a medical marijuana patient and does NOT use cannabis in any form.  He was diagnosed with schizophrenia about 20 years ago, and has taken 300mg of clozaril (clozapine) daily since.  He is not "symptom" free by a long shot, and struggles to live daily, and is reminded often by his prescribing physician that he should be happy and thankful for the quality of life his pharmaceuticals allow, because it is better than...no life at all.)  

He and I (we) deal daily with the debilitating positive and deficit symptoms of his "dis-ease" (despite his pharmaceuticals), and now, the long-term side effects of his medication, are killing him.  He has developed "metabolic syndrome" despite his living an otherwise hyper-healthy and focused life.  His body's metabolic systems, are failing him, and its because of his medicine. 

Something has to change. 

The price of his daily psychiatric medication (pills, required blood draws, doctors appointments, social/cognitive therapy sessions, etc.) is well over $2500 a month...probably nearly a million dollars so far, and i sincerely thank the good people of the United States of America and the Great State of Washington, for providing significant help with his expenses.   

His illness has wiped me out physically, emotionally, mentally, and financially.  I developed slow and debilitating chronic stress, chronic intractable pain, and depression, and became a bundle of symptoms I now recognize, in myself, as "endocannabinoid deficiency" (I'd used up all my body's natural cannabinoids, and didn't make enough anymore to maintain a healthy and vigorous life.)  In fact, my life was in serious jeopardy, and i was sternly warned to either relieve the stress in my home, or i would never see my 80th birthday.)

All that changed five years ago I chose cannabis as my medicine, rather than the pharmaceuticals offered (antidepessants, high blood pressure meds, group support therapy for families of schizophrenics, etc.)  Five years later I am healthy and vigorous again, and free of all my symptoms.  These days I have a cannabis cigarette at least once a day, just for the THC "reward" (it keeps me coming back), and some days i even break out my beautiful bong, or use my grandma's old pipe while i sit out on my deck and watch the sun set, but mostly i medicate daily with high THC sativa strains that i turn into edibles, oils, and creams.  Smoking anything isn't healthy, i know.   

But, for me, like for most cannabis patients, not just any marijuana will do!    In fact, if i use the wrong kind, it wrecks me.   I have to use the kind of cannabis that I can't get off the streets or through my over-18 grandson's connections, or even though my state's network of nonprofit medical cannabis dispensaries and coops. Today, I feel and look like i've lost 40 years, and my eyes sparkle with energy and hope again.  Cannabis has "rejuvenated" me.  I FEEL healed, and my doctor says i am...in fact, she says i'm the only patient she's ever seen who's over the age of 50, who isn't taking at least four complicating pharmaceutical drugs. She says I should just keep doing what i'm doing.  Thank you cannabis!

So naturally, i wondered if cannabis might help my beloved husband.  

Of course, his first and immediate choice is obvious: either

1. start taking about six more pharmaceuticals daily to treat the death-march of his "metabolic syndrome" side-effects (and, as his prescribing psychiatrist says, and be thankful that he might even get  another few years of "quality life.")  This choice would add another $1000 or so each month to the PRICE of his current medical/pharmaceutical treatment (which the people of the United States of America and the Great State of Washington have agreed to pay on his behalf, should he choose it);

 or,

 2.  do something else.

But, the research in this article suggests that if my beloved husband used MY cannabis medicine for HIS 'dis-ease" he would probably psych out and have to be heavily sedated and institutionalized for his own safety.  It is ironic that I need high-THC sativa strains for my particular cluster of "conditions," and he might need high-CBD indica strains, for his. 

Who'd have known?   We need to  find out!

Problem is, you just can't go out and "buy" marijuana off the street, and call it medicine.  One week you might get an ounce of someone's high-THC indica strain that was grown in a moldy garage and sprayed with insecticides, and next week you might get spice-laced brickweed grown on an abandoned chemical dump site in california.  To the street seller, and the black marketeer, these are all "good meds" and are exactly what you need!  No thanks.

I live in Washington state BECAUSE i can grow my own medical cannabis.
I think we all have the right to grow our own cannabis, just as we can all grow our own apples or tomatoes or garlic, and i think something stinky is happening when a government forbids it.  Cannabis will grow in every state in our union.  It has many uses besides as medicine.  No one has ever overdosed on cannabis, nor has anyone ever died as a result of using cannabis....the only cannabis deaths we've had are a consequence of the war on drugs.  Our prisons are FILLED with cannabis prisoners.

Here in Washington State, we embraced cannabis as medicine nearly two decades ago, and we have an active and intelligent medical cannabis community that's dedicated to diversity, honoring the individual, and helping each other out.   Recently, we Washington voters mandated that our state also facilitate "recreational cannabis" so that any adult in our state, regardless of their health, can partake of the re-CREATE-ional properties of cannabis, and be able to acquire it sanely and safely from government stores.  We are allowing our state to tax and regulate this recreational cannabis, as their reward for setting up and managing these pot shops, and we hope the revenue it generate fills the state's coffers so that we have plenty of money for more and better government services.  We also believe having recreational cannabis reasonably abd safely available to ANY adult, will reduce the devastating cost and consequences of alcohol abuse.   We're hoping our state figures out HOW to do all this, and soon, and that during its processes it doesn't lose sight of the medical cannabis patient, for whom "mcPot" brownies from the government potshops, will suffice.  Growing your own, is as therapeutic, as using it.

Washington State's highly networked and tremendously caring community of medical marijuana patients means I have access to the high-CBD cannabis strains that were used to treat schizophrenia in this study, should my beloved husband, so choose.  

So, kudos to the Germans (and other international researchers) who are helping "unlock" the imprisoned medicinal qualities of cannabis. 

Cannabis research like this, is prohibited in the United States. 

America needs to end cannabis prohibition. 

peace, plenty, prosperity
love,
ion magic

MarcyRogersP
MarcyRogersP

I read this article, just grasping at whatever may be available for the treatment of the relentless psychosis of schizophrenic or schizoaffective disorder that tortures my 34 year old son (and thus myself) 24/7.  He's on Zyprexa, after many others were ineffective.  This one is following in the footsteps of the others; not working much, as well as having caused extreme weight gain.  He also lives on an extreme amount of pain medication due to an artificial disc in his back that is, in short, a failed back surgery.  I've heard SO much that pot heals that I was hoping to read that possibly the cannabis oil (orally or locally applied) could alleviate a lot of the pain and in turn, help to lessen the psychosis.  Not that I KNOW that the reduction in pain would relieve the psychosis and anxiety, but it seems to me that it would be related. He certainly can't afford to "get high".  Heck, it's all he can do to keep ANY grasp on reality NOW.  I HAVE been concerned about the THC because of the loose grip of what is "the voice" in his head and what is REAL since the voice tells him horrible things, encouraging suicide and shows him images of things that my son says even HOLLYWOOD can't come up with!  I digress.... basically just wondering IS there somewhere to procure the correct part of cannabis, minus the THC and be SURE it's really what it's supposed to be. There's NO margin for error here.  He's VERY ill!  Any ideas are GREATLY appreciated! We DON'T live in a medical marijuana state, but I haven't heard of anyone who "dissects" the marijuana's components from normal dispensaries anyway!  Thanks..

Totallynothighrightnow
Totallynothighrightnow

The link between marijuana and schizophrenia. It's ironic. When a study was published showing an unusually high number of marijuana users having schizophrenia, the newspapers were chock full of claims that this was proof that marijuana usage caused schizophrenia. 

Now this study appears and... Oh the irony

ribama
ribama

It is great to hear about some more potential treatments that are natural. My wife takes a supplement called SBX that is natural and also Omega 3 (one high in EPA) this has worked beautifully for her but you hear very little about it.

J.c
J.c

@kirklazarus19  Hello, i have some questions can you please mail me please? 

Jearoycroes@gmail.com

Thank you a lot!!!

TyWorkman
TyWorkman

Can you inbox me? I have questions. Tyler42287@hotmail.com

SageCutely
SageCutely

@ionmagicWhat you're looking for your husband to use is Cannabidiol... or CBD.

Most strains these days are around 1% or less in CBD content (anti-psychotic cannabinoid) and up to 24% THC (the psychoactive cannabinoid).  There are quite a few people who have issues with these kinds of cannabis.

These kinds of cannabis a primarily a result of pressures on cannabis breeders that have come about from... PROHIBITION.  Of all places.   There's been an increase in incidences of "Cannabis Psychosis" because of these new strains of cannabis.

http://thecleangame.net/2013/10/prohibition-causes-psychosis/

I live in Colorado have been lucky enough to have been gifted with a cut of the "Harlequin" cannabis plant.  It's 8% CBD and only 6% THC and it won't get you 'high' or 'stoned' or 'whacked out' as you put it. :D

There are a number of other "High CBD" strains of cannabis out there... see if you can pick one up in your area.  I know I've been giving Harlequin to everyone I can find that needs it.

I wish you luck in Washington!


Keep it Clean! :D

justjoan
justjoan

@MarcyRogersP

Hi Marcy my son is schizoaffective also, so I feel you pain!!!!  Psychosis is a long horrible way for anyone to live!!!  My son finally got on antipsychotics like Zyprexa and others but was immediately put on Sustenna http://www.invegasustenna.com/ and still struggles with the voices but this he receives in a shot form every 3 weeks which has helped immensely.  His doctor is against him smoking pot because she says that he does not get the full affect of the drug, but he smokes pot and it really keeps him calm!  So kind of being stuck between a rock and a hard place.  All I can do is support my son, and I always will!!!!  I know it is extremely difficult at times, but I am not living in his world that he calls hell!!!!!  Hope this helps and I think it's worth checking out with your doctor!

CastEmCompany
CastEmCompany

@Totallynothighrightnow did you read the article? There is an isolated compound in marijuana that acts as an antipsychotic.  Most people who study cannabinoids are fully aware of this.  They also know that there are compounds in marijuana that are very bad for psychosis like THC.  There are two main cannibnoid receptors in the brain and one that gets binded acts as antipsychotic. Marijuana has a lot in it.