Marijuana

Here's another update of this post, to account for studies between 2009 and 2015.

Marijuana use is quite common in the university population I see in my clinic.

It is my opinion that sporadic recreational marijuana use is less dangerous than alcohol use, for many people.  For others, it is more problematic, and the risks may be underestimated. 

Cannabis is an acute intoxicant, which could make activities such as driving much more dangerous. Also, smoking marijuana undoubtedly causes harm to the lungs, though probably not quite to the same degree as smoking tobacco cigarettes (see references below).

There is strong evidence that marijuana use increases the risk of developing a psychotic disorder, probably by about 40%.

People who have a psychotic illness, or who have a family history of psychotic illnesses, are at higher risk for having new or continuing psychotic symptoms if they use marijuana.

Also, based on some of the evidence cited below,  children and adolescents are probably much more vulnerable to negative, long-term emotional and cognitive effects from marijuana use. 

Many regular consumers of cannabis have problems with motivation. This may be reflected in poor grades in school, lack of success in building a career, etc.  This is possibly a non-causal association, but if someone has low motivation to begin with, the addition of cannabis is not likely to help.

There may be some selected exceptions.  For example, some have claimed that a culture of cannabis use has had a catalytic role in helping reclusive technical geniuses relax their social and creative inhibitions, to permit some examples of very successful scientific and business innovation, such as in Silicon Valley.

There is strong evidence that marijuana use is associated with more severe psychiatric symptoms, of almost every type; but much of this association could be due to the fact that those with more severe symptoms are more likely to use marijuana, not the other way around. In any case, those who choose to use marijuana more regularly as a cultural pursuit may be surrounding themselves with others who have more severe symptoms.   This is similar to the case  of alcohol:  part of the harmful effect of drinking heavily is due to proximity to places (such as rough bars) where there are a lot of other heavy drinkers -- in this environment, there is likely to be more physical danger, and much less breadth of social or cultural opportunity.  Ironically, decriminalization should probably reduce this effect, and therefore reduce some of the potential social harms.

There is some evidence that marijuana or other cannabinoids could be helpful to treat a variety of medical ailments. This evidence needs to be taken seriously.

Here is a brief survey of the very large literature on this subject:

Evidence of Risk and Harm

     Psychiatric Risks

This 2007 review from Lancet shows convincing evidence that marijuana use increases the risk of developing a psychotic disorder, and that the risk is dose-dependent (i.e. the more marijuana one uses, the higher the risk is of developing a psychotic disorder):
http://www.ncbi.nlm.nih.gov/pubmed/17662880

It concluded that the evidence is less clear linking marijuana to other problems, such as depression and anxiety: many of the studies looking at this did not sufficiently address non-causal reasons for the association between marijuana and other problems. For example, people who are more depressed or anxious may have a higher likelihood of using marijuana to treat their symptoms. Or, people whose cultural style may lead them away from conventional treatments for depression, may be more likely to use marijuana regularly.    Use of psychotherapy and antidepressants are also more common among those with depression, but this does not prove that psychotherapy and antidepressants cause depression! 

In this 2008 review from the British Journal of Psychiatry, the authors conclude that marijuana use is associated with worse outcome in psychotic disorders--but they say that the existing studies show only an association, not causality. Once again, confounding variables may cause this association to exist:
http://www.ncbi.nlm.nih.gov/pubmed/18978312


A significant cannabis withdrawal syndrome is described in the literature, particularly for heavy, long-term users. The syndrome involves about 2 weeks of irritability, restlessness, and insomnia, which could be quite destabilizing for someone struggling with mood symptoms, therefore leading to continued marijuana/cannabis use. Here is a 2006 review of the subject:
http://www.ncbi.nlm.nih.gov/pubmed/16612207

A few recent prospective studies have demonstrated increased dysphoria, anxiety, tiredness, ideas of reference, and schizotypal symptoms as a result of marijuana intoxication. In particular, individuals with pre-existing schizotypal personality traits had a more substantial increase in schizotypal symptoms following THC exposure. This adds to an evidence base suggesting that marijuana use carries a significant risk of exacerbating a variety of psychiatric symptoms, particularly psychosis-spectrum symptoms, and particularly in those with risk factors for psychotic illness.
Here are the references, which are both from Psychological Medicine in 2009:
http://www.ncbi.nlm.nih.gov/pubmed/19017430
http://www.ncbi.nlm.nih.gov/pubmed/19335936

This interesting study involved administration of THC to healthy volunteers who did not use THC.  Some members of the cohort experienced transient psychotic phenomena, while others did not.  These differences were associated with differences in cognitive impairment and functional MRI results. This supports the common-sensical observation that some individuals may be more vulnerable than others, to having adverse neuropsychiatric effects from THC use.  
http://www.ncbi.nlm.nih.gov/pubmed/23020923


Many other studies looked at populations who used different amounts of marijuana over time, and compared them in terms of various symptoms and intellectual functions, etc. Unfortunately, I find this type of retrospective analysis to be weak, and highly prone to confounding variables. In order to understand marijuana's long-term effects for sure, we would need to do a long-term, prospective, randomized, controlled study.

     Physical Risks

Here are some studies looking at risk to the lungs associated with marijuana smoking:

These studies show an increased risk of lung cancer in marijuana smokers:
http://www.ncbi.nlm.nih.gov/pubmed/19057263
http://www.ncbi.nlm.nih.gov/pubmed/18238947

These studies show a likely causal association between long-term marijuana smoking and obstructive lung disease:
http://www.ncbi.nlm.nih.gov/pubmed/18238947

http://www.ncbi.nlm.nih.gov/pubmed/17666437

     Prospective Animal Studies

Animal studies could add a little bit more information into the picture, since these have been done in a prospective, controlled fashion. Here is what I've found from the animal research literature:

This study showed that chronic marijuana exposure impairs spatial memory & learning in rats:
http://www.ncbi.nlm.nih.gov/pubmed/19179850

This study showed that chronic marijuana exposure impairs social and cognitive functions in rats, but especially when the period of exposure is during the pubertal ("adolescent") phase of development:
http://www.ncbi.nlm.nih.gov/pubmed/18782382

Another study showing that marijuana exposure may be particularly harmful to the "adolescent" brain in rats:
http://www.ncbi.nlm.nih.gov/pubmed/15582916

This study from UBC suggests that high-dose cannabinoids increase emotionality and "sensitize the stress axis" in rats:
http://www.ncbi.nlm.nih.gov/pubmed/16442741



Evidence of Benefits or Therapeutic Uses

This study shows that a synthetic cannabinoid promotes neurogenesis in the hippocampus, and may have antidepressant and anxiolytic effects:
http://www.ncbi.nlm.nih.gov/pubmed/16224541

Here is a reference to a good 2008 review of the pharmacology and potential therapeutic applications of cannabinoids such as marijuana:
http://www.ncbi.nlm.nih.gov/pubmed/18482430


     Neurological Diseases


Here's a 2012 study showing relief in muscle stiffness in multiple sclerosis patients, due to cannabis administration:
http://www.ncbi.nlm.nih.gov/pubmed/22791906

Another 2012 study from CMAJ showing relief of spasticity and pain in MS patients, following cannabis administration:
http://www.ncbi.nlm.nih.gov/pubmed/22586334


This study shows immediate relief of the symptoms of Parkinson's Disease following cannabis treatment: 

http://www.ncbi.nlm.nih.gov/pubmed/24614667

     Bowel Disease

This study, from a major journal of gastroenterology, shows that cannabis dramatically improved symptoms  of Crohn's disease (a type of inflammatory bowel disease), in a prospective, placebo-controlled trial.  
http://www.ncbi.nlm.nih.gov/pubmed/23648372

Another prospective study, showing that cannabis improves quality of life in inflammatory bowel disease:
http://www.ncbi.nlm.nih.gov/pubmed/22095142

     Pain Disorders


Here's a good 2013 study showing that cannabis compares favorably with other standard pharmacological treatments for neuropathic pain:
http://www.ncbi.nlm.nih.gov/pubmed/23237736

     Heart Disease

This 2005 study from the prestigious journal Nature suggests that cannabinoids could reduce the progression of atherosclerosis (the main cause of heart disease):
http://www.ncbi.nlm.nih.gov/pubmed/15815632
 
Conclusions

In conclusion, I think that marijuana use is dangerous, and harmful to your health in a variety of ways, due to acute intoxication, increased risk of psychosis, possible cognitive side-effects, and lung damage. It may be particularly harmful to adolescents. As a cultural pursuit, it may distract people from other life activities, or meaningful life roles, just as any habit or addictive behaviour can. But it may have beneficial effects for a variety of medical problems.

I have to admit, to be fair, that some people have psychological benefits from marijuana use -- certainly there are many testimonial accounts of this, but evidence beyond this is not clear on this point.  The few studies touting this application tend to be of short-duration, which leads to a similar criticism as that pertaining to mainstream pharmaceuticals:  short-term benefits for symptom relief do not always translate into long-term benefits, if the use continues for years.   More research is needed to gain a better understanding of the potential risks or benefits of cannabinoids, especially over longer-term use.

I have certainly seen people for whom cannabis appears to have a better benefit:risk profile than alternative treatments, for example to treat chronic pain symptoms and associated insomnia.    It may be preferable to use cannabis instead of a benzodiazepine, opiate, pregabalin, etc., particularly if these latter agents are causing a much higher load of side effects in a given person.

For some people, cannabis could be a relatively harmless entertainment, or even a catalyst for enjoying life more richly in various settings.  In this way, it could be analogous to having a glass of wine with meals, etc.

Another angle to the analysis is to consider relative risks of cannabis compared to other accepted intoxicants, such as alcohol.  With this type of risk analysis, one could often see greater risks with alcohol compared to cannabis, on a case-by-case basis, but we don't have good group data on this.  Suppose we had two adjacent similar countries, and prospectively allowed free access to alcohol in one country, and free access to cannabis in the other.  Then, suppose we were to assess health outcomes in these countries 20 years later.  I suspect we would have more examples of ruined families, criminal assaults or manslaughter, chronic diseases, and traffic fatalities, in the "alcohol" country compared to the "cannabis" country. 

The issue is complicated by the fact that those who are more apt to use cannabis are statistically also more apt to use alcohol and other street drugs.  It is possible that cannabis use could have "gateway" effects, leading people into a higher-probability zone of trying or using more dangerous drugs. But this is an open question. 

A proliferation of cannabis dispensaries have appeared in Vancouver in the past year.  While I do think that legalization is a positive step, in terms of the various pros and cons for public health,  I am not happy with the idea being touted by some, that cannabis is some kind of health food, or panacea.   There is an issue of cultural freedom as well, which I support, though I think that many in this "4-20" movement have an exaggerated view of the benefits of cannabis, with an underestimation of risks.


 

Passion Flower

There's not a lot of research information about passion flower's medical effects.

It's a beautiful flower though! I would encourage having some in your garden if possible.

Here's a reference to a 2007 Cochrane review:
http://www.ncbi.nlm.nih.gov/pubmed/17253512

Passion flower is mentioned in a good 2006 review article on complementary medicines in psychiatry, from The British Journal of Psychiatry:
http://www.ncbi.nlm.nih.gov/pubmed/16449696

Here's a reference to a 2001 study from Iran, showing that passionflower relieved anxiety to a similar degree as oxazepam (a benzodiazepine), over a 4 week trial.
http://www.ncbi.nlm.nih.gov/pubmed/11679026

The same author published a study suggesting that passionflower could help with opiate withdrawal symptoms:
http://www.ncbi.nlm.nih.gov/pubmed/11679027

In conclusion, not a lot of evidence. The existing studies are only of short duration. But passionflower extract does look like an interesting substance to research further.

"Micronutrient Treatment"

There are examples of "micronutrient treatments" being marketed to help various mental health problems.

These treatments may be marketed aggressively: there may be slick internet sites, perhaps with an enthusiastic following of people who believe strongly in the product.

If the manufacturer of such a product is quoting "research studies," I encourage you to look carefully at the studies referred to. If you are seriously considering products of this type, I would suggest looking at the articles in their entirety at a library.

I encourage anyone interested in pursuing treatments of this sort to ask the following questions:

1) What type of evidence exists regarding effectiveness & safety? Is the evidence from large, double-blinded, randomized, controlled studies conducted by researchers who do not have financial connections with the manufacturer?

2) Is the research pertaining to the product published in a journal with high scientific standards? (In order to answer this question for yourself, I would invite you to leaf through numerous issues of the journal, and compare this with an independent, peer-reviewed journal such as Lancet or The New England Journal of Medicine).

2) Is the evidence mainly from enthusiastic testimonial accounts or case studies? Is this type of evidence reliable enough for you?

3) How much money is required to purchase the treatment? Does the manufacturer encourage you to involve yourself in a long-term financial commitment?

4) After acquainting yourself with common sales and marketing tactics (for a primer on this subject, see Robert Cialdini's book, The Psychology of Persuasion), do you see evidence of highly persuasive or biased sales tactics being used in the marketing of the product? Are vulnerable people being taken advantage of in the marketing of the product?

Have a look at this link, which gives a brief history and overview of charlatanism--being familiar with this history may allow you to make more informed choices about your own medical care:
http://en.wikipedia.org/wiki/Quackery

I do not mean to single out alternative remedies in this post--I encourage the same critical standards to be applied regarding all types of therapy. Mainstream pharmaceutical manufacturers and other providers of mainstream therapies may often be guilty of devious marketing behaviours. In my opinion, though, mainstream pharmaceutical manufacturers have a much harder time getting away with overt charlatanism at this point, compared to many manufacturers of alternative remedies.

Also, I wholeheartedly acknowledge that there can be alternative remedies which are helpful, and which are marketed ethically.

Here in Canada, we live in a free society, with a strong emphasis on freedom of speech. Imposing more strict legal restrictions or regulations upon health choices would limit freedom. I support maintaining a free society, but the presence of charlatanism is one of the costs of this freedom.

Inositol

Inositol is chemically similar to glucose (the type of sugar required by the brain for energy). It is a precursor in a so-called "second messenger system," which cells require to communicate with each other. In the brain, these second messenger systems are activated by various neurotransmitters including serotonin. There is some evidence that brain levels of inositol are reduced in depression and anxiety disorders. Inositol is present in a typical diet, in amounts of about 1 gram per day. Doses of supplemental inositol are typically 10-20 grams per day.

A Cochrane review from 2004 concluded that there was no clear evidence of supplemental inositol being beneficial in the treatment of depression:
http://www.ncbi.nlm.nih.gov/pubmed/15106232

Here's a 2006 reference from Bipolar Disorders showing that supplemental inositol could help treat bipolar depression in some patients already taking lithium or valproate. In 4 out of 9 patients taking 6-20 grams per day of inositol, their depression substantially improved over 6 weeks, with continuing improvement over an additional 8 weeks. However, the other 5 out of 9 patients either did not improve, or actually had worse symptoms. The patients who got worse had more manic or irritable symptoms at the beginning of the trial. When the results were averaged, the inositol did not appear to help significantly--however, it is notable that a subgroup of patients appeared to benefit significantly.
http://www.ncbi.nlm.nih.gov/pubmed/16542187

This 2001 study from the Journal of Clinical Psychopharmacology compared 1 month of inositol (up to 18 grams per day) with fluvoxamine (up to 150 mg per day) in the treatment of panic disorder. Both groups improved similarly. The fluvoxamine group had more side effects of tiredness and nausea. The study is limited by its short duration.
http://www.ncbi.nlm.nih.gov/pubmed/11386498

This 1995 study from the American Journal of Psychiatry compared 12 grams per day of inositol with placebo, for one month, in the treatment of panic disorder. The authors conclude that inositol was effective with no significant side effects. Mind you, when eyeballing the chart of data from individual patients, the results did not look very impressive.
http://www.ncbi.nlm.nih.gov/pubmed/7793450

Here's a negative study, showing no difference between inositol and placebo, when added to antidepressant therapy for OCD:
http://www.ncbi.nlm.nih.gov/pubmed/11281989

The same author as above published a study in 1996 showing that inositol on its own was superior to placebo for OCD treatment. However, despite "statistical significance" being found, eyeballing the data from each patient (presented in the body of the paper) reveals doubtful clinical significance (that is, the amount of benefit looked quite unimpressive to me):
http://www.ncbi.nlm.nih.gov/pubmed/8780431

Here's a reference to a 2001 study showing that inositol was superior to placebo in treating binge eating and bulimic symptoms. In this case, I found the data to be clinically significant. However, the study was limited by its small size.
http://www.ncbi.nlm.nih.gov/pubmed/11262515

Here's a small 1995 study showing that 4weeks of inositol (12 grams per day) was superior to placebo in treating depressive symptoms. The data appeared clinically significant, though modest.
http://www.ncbi.nlm.nih.gov/pubmed/7726322

Here's a 2004 reference from a dermatology journal showing that inositol supplementation led to improvement of psoriasis in patients taking lithium:
http://www.ncbi.nlm.nih.gov/pubmed/15149510

In conclusion, inositol may be modestly effective for treating anxiety, eating disorder, and depressive symptoms. It may perhaps be quite variable in its effectiveness, i.e. some individuals might have much more benefit than others. It appears to be well-tolerated with few side-effects. I could not find good data on long-term safety though. The quality of the evidence is not very robust-- the studies have involved only small numbers of patients, for short periods of time. More research is needed.

Kava

Kava is a perennial shrub native to islands of the South Pacific. It has been ingested there as part of local culture. It has a relaxing effect.

Kava has been associated with liver toxicity: there have been cases of liver failure necessitating liver transplant, and there have been fatalities. As a result, the sale of kava is restricted in Canada.

Here is a reference about the liver toxicity issue:

http://www.ncbi.nlm.nih.gov/pubmed/15068826

In this 2008 article from a liver disease journal, cases of kava toxicity are reviewed. It is concluded that liver damage is a rare side effect of kava. It also found that many of those experiencing liver toxicity had used higher doses of kava, for longer periods of time, than recommended.

http://www.ncbi.nlm.nih.gov/pubmed/18989142

Effectiveness:

Here is a 2009 prospective, randomized, controlled study from Australia, in which 3 weeks of kava treatment (250 mg kava lactones per day) had minimal side-effects and led to substantial, clinically significant improvements compared to placebo in generalized anxiety symptoms and depressive symptoms:

http://www.ncbi.nlm.nih.gov/pubmed/19430766
As a critical commentary here, I think that 3 weeks is a VERY short study period, and therefore has limited clinical relevance. A great many approaches can relieve anxiety over a brief period of time (e.g. benzodiazepines); it's of much greater interest to see what happens after 3 months, or after 3 years!

Here is a 2003 Cochrane review, showing significant benefits in anxiety symptoms from kava treatment:

http://www.ncbi.nlm.nih.gov/pubmed/12535473

Here is a negative study from 2005, which showed that neither valerian nor kava differed from placebo in relieving anxiety or insomnia. The study participants were recruited on the internet, and were sent the blinded medication or placebo through the mail (another example of an interesting new study design):

http://www.ncbi.nlm.nih.gov/pubmed/16010204

In conclusion, kava seems promising as a treatment for anxiety. But there appears to be a small risk of very dangerous liver toxicity. It will require ongoing study to clarify risks vs. benefits, or to discover ways to minimize the risk of liver damage.

Valerian

Valerian is a perennial flowering plant native to Europe. Its sweetly-smelling flowers have been used to make perfume. Extracts from valerian root have been used as natural remedies in the treatment of insomnia and anxiety since ancient times.

Here is a review of the evidence:


This is a reasonably-done randomized 2009 study showing no effect of valerian vs. placebo in arthritis patients with insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/19114414

This interesting 2007 study--in which subjects were recruited via a TV health program, randomly mailed placebo or valerian, with results collected on-line--showed a very slight improvement in symptoms with valerian, with no differences in side effects, compared to placebo. Subjects in the valerian group took 3600 mg of Valeriana officinalis one hour before bedtime, for 14 days. Perhaps the most significant bottom-line result from the study to report here is that 9.1% of the valerian subjects reported feeling "better or much better", compared to 3.7% of the placebo subjects, after the end of the study period.
http://www.ncbi.nlm.nih.gov/pubmed/17940604


Here is a 2007 review from a sleep medicine journal, concluding that valerian is safe but not effective in the treatment of insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/17517355


Here's a 2006 Cochrane review, showing no evidence of valerian helping with anxiety disorders (mind you, the amount of data is very small):
http://www.ncbi.nlm.nih.gov/pubmed/17054208

Here's one positive 2005 study from Sleep, showing a modest benefit in sleep parameters and quality of life, from 28 days of a valerian-hops combination, compared to placebo, in the treatment of mild insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/17054208

Here's an interesting reference suggesting that valerian could have been the first treatment for epilepsy: but its potential benefit would have been extremely inconsistent, and at this point it is certainly not a practical treatment for epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/15509234

There are some other articles of dubious quality, which I found in some of the herbal medicine journals.

There could be dangerous interactions between valerian and other medications:
This is a case report of side effects with valerian + lorazepam:
http://www.ncbi.nlm.nih.gov/pubmed/19441067


In conclusion, I am not impressed with the evidence about valerian. It does appear to be quite safe. Mind you, there does not appear to be a good evidence base about possible dangerous interactions with other compounds. I recommend avoiding it, or using it with extreme caution, if you are taking other psychotropic medications. It may have modest benefits for some people, but for the vast majority the evidence suggests that it does not differ from placebo.

Valerian-based perfumes or scented oils might be pleasant and safe to use as aromatherapy for insomnia or anxiety, in conjunction with other relaxing activities.

Herbal Supplements & Vitamins

I'm starting a series of posts based on some questions that were sent in by a visitor (A.E.).

Here's the first question:
1. Herbal supplements and vitamins: What are your views on therapeutic value of multivitamins, Valerian, Kava, Inositol, Passion Flower, and so on?

-I think the risk:benefit ratio of multivitamins is quite favorable. I've written a few other posts about vitamins. With respect to mood or brain function in general, there may be particular benefit from folic acid, thiamine, and higher doses of vitamin D. Standard dose vitamin-mineral supplements are probably harmless at worst (as long as you get a good-quality brand--there's some evidence of dangerous impurities such as lead, in some ). Many people have poor diets, and a supplement could at least help prevent deficiencies in vitamins and iron which may further obstruct recovery from mental health problems. Supplements should not be a substitute for improving the healthiness of one's overall diet (you still need to eat your vegetables even if you're taking vitamins!)

Selling supplements is a huge business: the world market has about $180 billion of annual sales, and is rapidly growing (reference: http://www.nutraceuticalsworld.com/articles/2008/04/dietary-supplements-the-latest-trends-issues).
This is comparable in size to the $440 billion annual market size of the pharmaceutical industry (reference: http://www.valuenotes.com/Prabhudas/pl_pharma_31Mar09.asp?ArtCd=143465&Cat=I&Id=12).

I think we need to be wary of the sales tactics that go on in the dietary supplement business, especially since the quality of research in this area is, for the most part, quite primitive. If you walk into the nutritional supplement area of a health food store or pharmacy, you may be bombarded with advertising, possibly a sales person offering you attention, concern, and apparent expertise--and all of this is in the context of all sorts of other obviously healthy things, perhaps organic vegetables, right next to you. It is a biased environment. Proximity to healthy food and healthy people does not constitute evidence of effectiveness! Yet, there are some supplements that could be helpful. Just be wary of the hype, pseudo-scientific claims, and sales jargon, etc.

I'll write separate posts about valerian, kava, passion flower, and inositol.

In the meantime, here's a reference to a 2006 review in The British Journal of Psychiatry about complementary medicines in psychiatry. I recommend having a look at the whole article at a library:
http://www.ncbi.nlm.nih.gov/pubmed/16449696

St. John's Wort

St. John's Wort is a herbal antidepressant. Its mechanism is not well-understood, and at this point is in the realm of speculation, but may involve multiple compounds rather than just a single ingredient (one of the many ingredients in St. John's Wort extracts, for example, is hyperforin).

There is an evidence base in the research literature, supporting its use. However, I find many of the articles to be published in minor journals, and to be of questionable quality.

I will restrict my present survey to a few studies that I consider to be of higher quality:

Here is an article abstract discussing possible mechanisms of action:
http://www.ncbi.nlm.nih.gov/pubmed/12775192

This is a reference to a Cochrane review from 2008.
http://www.ncbi.nlm.nih.gov/pubmed/18843608

It supports the use of St. John's Wort for treating major depression, and concludes that response rates were similar, compared to SSRIs and tricyclic antidepressants. It also concludes that St. John's Wort was much better-tolerated than other antidepressants, with a greatly reduced risk of side-effects or of discontinuing the medication due to side-effects. The authors note that studies from German-speaking countries tend to report a greater benefit from St. John's Wort.

I note that this review was written by authors from a "Centre for Complementary Medicine Research" in Germany. It may be that researchers at such a site could have a biased view in favour of complementary therapies.

This review from the major journal BMJ in 2005 gives much less enthusiastic conclusions about St. John's Wort:
http://www.ncbi.nlm.nih.gov/pubmed/15684231

It gives a rigorous analysis of the data, and concludes that there is evidence, mainly from older, smaller, lower-quality studies, that St. John's Wort is beneficial compared to placebo, particularly for mild to moderate depression. More recent, larger, more rigorous studies, and studies including patients with more severe depression, show smaller treatment effects.

It does strongly emphasize that different preparations of St. John's Wort may differ in quality, especially since it is an over-the-counter product in most places, and therefore may lack the guaranteed quality control of regulated pharmaceutical products.


Here are links to 2 carefully done studies from 2001 and 2002, published in JAMA, showing no therapeutic benefit of St. John's Wort. The first study compared only with placebo, the second study also compared with sertraline, an SSRI--in the latter study the sertraline actually didn't do well against placebo either! I have to wonder if particular samplings of depressed patients are relatively less treatment-responsive compared to placebo, for a variety of reasons. Also, it may be that some preparations of St. John's Wort are more effective than others:

http://www.ncbi.nlm.nih.gov/pubmed/11308434

http://www.ncbi.nlm.nih.gov/pubmed/11939866

Here is a link to a recent German study showing that people who respond to St. John's Wort have lower rates of relapse, compared to placebo, if they continue to take it for a year:
http://www.ncbi.nlm.nih.gov/pubmed/18694635


There are some interactions St. John's Wort may have with other drugs; mainly the concern is that St. John's Wort induces the liver to metabolize other drugs more actively, therefore reducing the levels of other drugs. This could be a danger for some people. Here is a reference about this:
http://www.ncbi.nlm.nih.gov/pubmed/15260917

There are case reports of St. John's Wort causing mania, so it would need to be used carefully in persons with bipolar disorder. But there are no studies that I can find, which give clear estimates of risk for St. John's Wort to cause mania or rapid cycling, particular when compared to other treatments for depression in bipolar disorder.

There is a poor evidence base looking at the safety of combining St. John's Wort with other antidepressants, but there are a few case reports of possibly dangerous states such as serotonin syndrome.

I will add to this posting later, but for now I would say that St. John's Wort is probably quite safe for most people, and is probably easier to tolerate (in terms of side-effects) than prescription antidepressants. It may be effective, for some people, to treat or reduce symptoms of depression and anxiety. It may reduce levels of other medications, including contraceptives, and may interact with other drugs, so these possibilities have to be considered very carefully, and discussed with your prescribing physician.

Also, I should add that different brands of St. John's Wort may differ in quality, differ in the extraction method used, etc. So if you are going to give St. John's Wort a try, it may be worthwhile to try several different brands. Given the abundance of positive research studies from Germany, it might be worthwhile to try a German brand.