CBD increases serotonin levels

Can THC and CBD replace antidepressants?

Cannabis for Depression - History

Can THC and CBD replace antidepressants and are they a natural antidepressant? To answer this question, we have to look back a few centuries, even millennia. Cannabis has been used for centuries to treat depression and anxiety. As early as 1621, the English clergyman Robert Burton declared that cannabis was helpful in treating depression. Cannabis was also used in India over 400 years ago and British doctors very often prescribed cannabis for depression in the 17th century.

More about antidepressants, depression and medicinal cannabis.

In 1890, the British doctor JR Reynolds analyzed the use of cannabis over the past 30 years and found that the long-term use of cannabis against depressive symptoms had a positive effect. And new studies also indicate that cannabis has an antidepressant-like effect in low doses. If this research is carried out further, a medically effective antidepressant with few side effects could perhaps one day be developed from it.

Antidepressants are being prescribed more and more often

Depression is a widespread disease, as more and more people suffer from this serious mental illness. According to the World Health Organization (WHO), more than 320 million people worldwide suffered from depressive disorders in 2015. Ascending trend. In Germany, too, more and more people are being diagnosed with “mental illness”. According to the health insurance companies, they are responsible for around a fifth of the days lost. Much too quickly, specialists, but also general practitioners, resort to the prescription pad and prescribe antidepressants, but these are not harmless "lucky pills".

According to the statistics portal, more and more antidepressants are being prescribed in Germany. The prescriptions of antidepressants for the treatment of depression rose by 50 percent from 2008 to 2017.

It also says that there is criticism for this development from many sides, including from the Deutsches Ärzteblatt. In addition, it is said that the drug supply is only one-sided. Outpatient psychotherapy is used too seldom, which does not correspond to the medical guidelines.

Those with statutory health insurance have to wait a long time for a free therapy place with a psychologist.

Why are no psychotherapies used?

It is very surprising that various health experts keep pointing out that outpatient psychotherapy is used too seldom, because the biggest problem is that there are simply too few free therapy places at health insurance therapists. People with mental health problems who urgently need therapy usually have to wait weeks, if not months, for a vacancy. While waiting, many get so sick that they have to go to the hospital.

Even the new guideline from 2017 could not accelerate access to psychotherapy. With this new reform the associations of statutory health insurance physicians and the medical organizations were obliged to offer appointments with statutory health insurance therapists. The maximum waiting time should be four weeks. One year after the introduction, questions about a psychotherapist at the appointment service points are among the most important inquiries.

“Of these 190,000, around 50,000 were inquiries about psychotherapist appointments. So they have lifted themselves to the top of the demand right from the start. Against the background of one billion doctor-patient contacts, that is little, but at least: The demand for psychotherapeutic appointments has been most pronounced here at the appointment service centers, "explained Roland Stahl, spokesman for the National Association of Statutory Health Insurance PhysiciansMedia report.

Most of them do not know the service points for making appointments

Many patients with statutory health insurance do not even know these service points for arranging appointments, it continues. Another problem is that usually only an initial interview is arranged, which has been mandatory since April 2018. This is the only way to get short- or long-term therapy for those affected.

“Initial discussions are clear for most of them. And then you always come across these waiting lists, which then start from six months and go over a year. During this time you feel like you have given up on yourself. And then you have no motivation to keep looking because you know: it will be the same with the next one, ”reports Maike Klossek.

Cash register therapists sue against appointment brokerage procedures

According to the reform, the service points should arrange two to five initial discussions (introductory hours) before the actual therapy begins. The Association of Statutory Health Insurance Physicians has now sued against this "additional" task.

“According to a decision by the Federal Arbitration Office in November of last year, the appointment service points should also arrange the so-called probatory meetings. But we as KBV have sued against this and this suit has a suspensive effect. We did that because, from the point of view of the legislature, it was not the mandate of the appointment service centers to arrange all appointments. So here the regular routes should actually be sufficient, ”said spokesman Roland Stahl.

Regardless of whether with reform or without, the regular route means long, long waiting times for sick people. The demand is high, the supply is too low. However, the spokesman for the Association of Statutory Health Insurance Physicians sees it differently.

“If I put on the nationwide glasses here, the care centers will be occupied by psychotherapists, all of them. 1,300 new seats have been created in the last few years. This made psychotherapists the fastest growing group in medical care, ”said Stahl.

Further problems when looking for a therapy place

In the 5th Social Code it is stipulated that those affected may also go to private therapists if the statutory health insurance companies cannot arrange a place with a health insurance provider. For this, the patients have to prove that the waiting times at the therapists in the vicinity are unreasonable. If the private therapy then complies with the guidelines, the health insurance company has to cover the costs.

Felicitas Bergmann led an information event at the conference of the German Society for Behavioral Therapy in Berlin in March 2018. She explained that the waiting times for private therapists are much shorter, but the health insurances are stonewalling.

“He may have a place available in the near future, but the health insurances are currently refusing to cover the costs across the board. That means, the patients are sent back to a consultation with a licensed therapist, and the whole thing is going in circles at the moment. I've heard of patients who have had to attend ten or more consultations. And just imagine: Telling a stranger your story ten times. Got no help ten times. Not only are the patients frustrated, so are we therapists. We would like to help, but we have to send the people on, ”said Bergmann.

Of course, the health insurance companies deny that they reject the reimbursement of costs across the board. For example, the Barmer-Ersatzkasse carried out:

“The aim of the reform from April 2017 to provide better patient care requires [...] a different approach to requests for reimbursement. Of course, the peculiarities of an individual case are still included in our decision. Therefore, if the relevant criteria are met, we may also reimburse further costs for treatment by a non-contractual provider. "

However, since the therapists have different experiences, they now plan to document the refusals under the name “Kassenwatch”. Then they want to complain to the Federal Insurance Office.

More on the subject of finding a therapy place.

There are several antidepressants available.

What antidepressants are there?

In the case of antidepressants, the following classification is made based on their chemical structure and the mode of action on the respective transmitter systems:

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants (e.g. opipramol, amitriptilyn or doxepin) act to varying degrees on the serotonergic and noradrenergic systems and have three carbon rings in their chemical structure. The substances thus intervene in several neurotransmitter systems at the same time and have a calming, mood-enhancing, anxiety-relieving and tension-relieving effect. The prescription is therefore mainly used for obsessive-compulsive disorder, anxiety and panic disorders.

In terms of side effects, a distinction must be made between acute side effects at the start of treatment and chronic side effects during long-term therapy. Tricyclic antidepressants can cause the following symptoms:

  • Dry mouth
  • Voiding disorders
  • Tachycardia
  • increased cardiovascular risk
  • Orthostasis syndrome (drop in blood pressure)
  • Worsening of pre-existing heart failure
  • Disturbance of the cardiac conduction system (T waves in the ECG)
  • The following side effects can occur with long-term treatment:
  • tremor
  • Visual disturbances
  • constipation
  • psychological alterations (e.g. delirious states)
  • allergic reactions (rare side effect)
  • Bone marrow damage (rare side effect)
  • Liver damage (rare side effect)

Tetracyclic antidepressants

Tetracyclic antidepressants are quite new psychotropic drugs that are a further development of the tricyclic antidepressants. Although both drugs are similar, tetracyclic psychotropic drugs have four instead of three carbon rings in their chemical structure.

In addition, they are assigned to the group of noradrenergic and specifically serotonergic antidepressants (NaSSA), as they have a stronger effect on the noradrenaline metabolism. The drug mirtazapine belongs to this group, the action of which is based on the postsynaptic 5-HT2 and 5-HT3 receptors.

Tetracyclic antidepressants can also have side effects. These include:

  • Dry mouth
  • Weight gain
  • a headache
  • Dizziness and tremors
  • Drop in blood pressure
  • Nausea and vomiting
  • diarrhea
  • skin rash
  • Confusion and fear
  • insomnia
  • Listlessness
  • Joint and muscle pain
  • Water retention in arms and legs

Occasionally, you may also experience the following symptoms:

  • nightmares
  • Restlessness
  • Anxiety
  • nervous discomfort
  • Numbness in the mouth

Selective Serotonin Reuptake Inhibitors (SSRIs)

Serotonin reuptake inhibitors are among the new antidepressants that intervene in the serotonin metabolism. However, the mood-enhancing effect of SSRIs only occurs after about two weeks. The antidepressants (e.g. citalopram, sertraline, escitalopram, fluoxetine) are prescribed for depression, anxiety and obsessive-compulsive disorders. They are also used for mental illnesses such as borderline personality disorder or bipolar disorder.

Compared to other drugs for depression, selective serotonin reuptake inhibitors are said to be. Nevertheless, nausea, headaches, restlessness, sleep disorders and digestive problems can occur at the beginning of treatment. In addition, SSRIs can trigger irreversible sexual dysfunction such as erectile dysfunction or anorgasmia.

In addition, with long-term treatment there is a risk of developing osteoporosis as serotonin acts on the osteoclasts and osteoblasts. Far more dangerous, however, is that taking SSRIs can increase the risk of suicide. Corresponding information had to be included in the instruction leaflet.

Selective norepinephrine reuptake inhibitors (NARI)

NARIs are often used in very depressed people. These psychotropic drugs develop their effect selectively on the so-called norepinephrine transporter in the brain. This means that they bind to the noradrenaline transporter in the central nervous system and thereby inhibit the reuptake of this neurotransmitter. This increases its concentration in the synaptic gap. But here, too, there can be unpleasant side effects such as dry mouth, restlessness, sleep disorders, feeling cold and loss of appetite.

Selective serotonin norepinephrine reuptake inhibitors (SSNRIs or SNRIs)

As a synthetic antidepressant, SSNRIs intervene in the serotonin and noradrenaline metabolism. This group includes, for example, the active ingredient venlafaxine, which unfolds its antidepressant effect in the central nervous system. In addition, serotonin-norepinephrine reuptake inhibitors are also prescribed against anxiety disorders and panic states.

Here, too, it is often stated that the SSNRIs have fewer side effects. However, they can still cause headaches, loss of appetite, insomnia, weakness, and nausea.

Monoamine oxidase inhibitors (MAOIs)

MAOIs are synthetic antidepressants that are used to treat depression. They work by blocking the monoamine oxidases. These are enzymes that break down monoamines such as norepinephrine, dopamine and serotonin and reduce signal transmission in the brain. As they inhibit the breakdown enzymes, the monoamine concentration increases. MAOIs are usually only used for severe, atypical depression when other antidepressants have failed. A mild depression, however, is usually not treated here.

However, monoamine oxidase inhibitors are anything but low in side effects. You may experience high blood pressure, dry mouth, headache and dizziness, among other things. In addition, a strict diet must be adhered to. Food such as red wine, chocolate or grapes can have life-threatening consequences.

What do antidepressants do?

When it comes to the effectiveness of these medicinal products, a large meta-analysis from 2008 is often cited. On the basis of 35 published and unpublished studies by the US FDA, it came to the conclusion that the newer drugs against depression are no better than in placebo groups and only have an effect on very severe depression.

The different active ingredients have been compared with one another in numerous studies. For people who have moderate to severe depression, these indicate:

  • In 20 to 40 out of 100 people who took placebos, their depressive symptoms improved within six to eight weeks.
  • In 40 to 60 people who received an antidepressant, the symptoms improved within six to eight weeks.

This means that only an additional 20 people who received an antidepressant showed improvement.

Also of interest is a 2001 study published in the British Medical Journal. Paroxetine and imipramine were rated here as very effective for adolescents. However, data was withheld and falsified here.

The study was funded by the pharmaceutical company Glaxo-Smith-Kline (formerly Smith-Kline-Beecham). The two antidepressants paroxetine and imipramine were compared with a dummy drug in 275 adolescents between the ages of 12 and 18 years. The result was that the drugs were generally well tolerated and effective.

Only after years of disputes were the original data, which had been withheld for a long time, released piece by piece. Researchers from the US and UK show that imipramine and paroxetine are no more effective than given a placebo. Nor can one speak of a “good” tolerance. Paroxetine led to suicidal tendencies, behavioral problems and other severe restrictions. Imipramine also triggered cardiac arrhythmias.

Current study on the effectiveness of synthetic antidepressants

British researchers published the results of their analysis last year. The researchers analyzed 522 studies on 21 antidepressants in which the test subjects were given either an antidepressant or a placebo. Although the researchers concluded that the drugs worked better than placebos, most of the subjects suffered from accompanying symptoms. In addition, the drugs do not help everyone.

“Antidepressants are effective drugs. But unfortunately about a third of patients with depression do not respond to the drugs, ”said lead author Andrea Cipriani from the University of Oxford.

She went on to explain that the treatment options had to be improved, as the effect was “overall small to moderate”. Another problem is that this study cannot answer some questions, such as which medication is better for treating therapy-resistant depression. There is also no breakdown of people by gender and age, so that no adapted recommendations could be derived from this.

Alicia Baer from Charité Berlin and Prof. Dr. med. Bschor from the Berlin Schlosspark Clinic in hersElaboration.

What are withdrawal symptoms?

Those who tolerate the antidepressant drug treatment well and take it for a longer period of time may have difficulty stopping it. Because then the so-called withdrawal symptoms can occur.These range from headaches and numbness in the extremities to flu-like symptoms. However, this term has been contested for a long time. Because this can downplay the symptoms. For this reason, many medical professionals are now advocating the use of the term “withdrawal symptoms”. The symptoms are similar to those when you stop taking addictive substances, as McGill University also explains, for example.

Withdrawal symptoms are also among the criteria for whether there is a drug addiction. As early as 2003, the World Health Organization pointed out in its report that doctors and medical professionals had reported withdrawal symptoms to the responsible authorities for antidepressants, in particular for selective serotonin reuptake inhibitors (SSRIs). Symptoms or problems were also reported that met numerous criteria for true drug dependence. If you look at current studies, they show the extent to which the “withdrawal syndrome” can assume. For example, researchers at the University of Auckland in New Zealand found that three quarters of people given SSRIs experienced withdrawal symptoms.

Drug interactions

Antidepressants are prone to interactions with other drugs and substances. For example, taking St. John's wort and SSRIs at the same time can lead to the development of serotonin syndrome. This also applies to the combination of SSRI and SNRI. Serotonin syndrome is triggered by excessively high levels of serotonin in the central nervous system. In the worst case, this can be fatal, which is why great caution is required here.

In addition, there may be interactions with numerous other drugs, such as antibiotics or beta blockers. The attending physician should therefore be informed if additional drugs are being taken.

One substance that can cause dangerous interactions is alcohol. Mixed consumption can unpredictably increase or decrease the effect of the drug. For your own safety you should therefore refrain from consuming alcohol.

Medicinal cannabis can be an alternative to antidepressants.

Can medicinal cannabis replace an antidepressant?

Studies have shown that cannabis can have antidepressant effects in low doses. Similar to the SSRIs, the THC increases the serotonin concentration in the brain. Scientists assume that this mechanism of action is due to the fact that the cannabinoids from the cannabis plant are similar in structure to the body's own cannabinoids.

The body releases endocannabinoids, for example, when pain or stress is experienced. In order to interact with the brain, the body has cannabinoid receptors. It is believed that the cannabinoid receptor CB1 has a direct influence on serotonin production.

A medical examination from McGill University in Montréal is particularly noteworthy. Researchers found that low doses of THC increased serotonin levels and that higher doses of THC lowered serotonin levels.

In one experiment, they forced laboratory rats to swim for 15 minutes. When they were given the synthetically produced cannabinoid WIN55,212-2, the rats swam significantly longer and looked for a way out. In contrast, the rats gave up more quickly without the cannabinoid administration. Serotonin levels were also significantly higher in the rats that received cannabinoids. However, this only applied to low doses of cannabinoids. The effect was reversed when the rats were given a higher dose of cannabinoid.

There are also studies that deal with cannabidiol (CBD). CBD is a non-psychoactive cannabinoid found in the cannabis plant, and researchers from the Federal University of Rio de Janeiro studied its anti-anxiety and antidepressant effects in animal models. Here, too, positive results were achieved. Researchers at the Universidad de Cantabria in Spain came to the same conclusion. The result is that CBD could be helpful against depressive disorders because it docks with the serotonin receptor (5-HT1A) in the brain.

Summary: is medicinal cannabis the alternative?

Let's summarize: The statistics show that the number of prescriptions for antidepressants continues to rise. In 2016 alone, for example, the antidepressant citalopram was the most frequently prescribed psychotropic drug with 290 million daily doses, according to the drug prescription report. And that - although psychotherapy should be the first treatment of choice. In addition, especially if the symptoms are severe, supportive antidepressants can be prescribed. The problem, however, is that there are too few free therapy places and those affected have to wait several weeks, if not months, for a place. And what should help in the meantime? Antidepressants, of course.

The effectiveness of antidepressants has been debated for years. Some studies and analyzes show that they are effective, others show that they are no better than a placebo. The whole thing is overshadowed by the possible side effects, which in extreme cases are hazardous to health. And last but not least, withdrawal symptoms can occur, which are wrapped up by specialists in the cloak of withdrawal symptoms.

So what does it take to end this dilemma?

Because in view of the fact that more and more people are suffering from a mental illness such as depression or anxiety, drugs whose effectiveness has not been clearly proven and can also have severe side effects cannot be the final solution. Of course, these drugs are also justified and can also be helpful in many cases. However, those affected should receive rapid psychotherapeutic help and medicinal alternatives.

Here, too, medicinal cannabis is not a one hundred percent solution that can "cure" a mental disorder. It is just an alternative - just like other herbal medicines that can be used in addition to therapy. Unfortunately, research on this is still in its infancy and it cannot be said for sure that cannabis for medicinal purposes or cannabis medication can relieve symptoms. However, the current study situation gives hope.


Note: In this article we report on prescription CBD or cannabidiol. This article makes no suggestion as to the possible purpose. Promises of use are left to the pharmacists.



  • Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (Universidad de Cantabria, CSIC, SODERCAN), Departamento de Fisiología y Farmacología, Universidad de Cantabria, 39011 Santander, Spain, 2016, Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5- HT / glutamate neurotransmission: role of 5-HT1A receptors