CBD and Depression

Each year, millions of people are prescribed anti-depressants to combat depression, but many find these pharmaceuticals affect their personality and general alertness to the point of lethargy, so they are turning to an alternative: CBD.

CBD or cannabidiol is one of 113 known chemical compounds that comprise the cannabis family of plants.

Among the more common cannabinoids are:

  • THC (tetrahydrocannabinol)
  • CBD (cannabidiol)
  • AM-2201 – synthetic cannabinoid
  • CBC (Cannabichromene)
  • CBCA (Cannabichromenenic acid)
  • CBCV (Cannabichromevarin)
  • CBCVA (Cannabichromevarinic acid)
  • CBD (cannabidiol)
  • CBDA (cannabidiolic acid)
  • CBDV (cannabidivarin)
  • CBDVA (Cannabidivarinic acid)
  • CBE (cannabielsoin)
  • CBG (cannabigerol)
  • CBGA (Cannabigerolic acid)
  • CBGM (cannabigerol monomethyl ether)
  • CBGV (Cannabigerivarin)
  • CBGV (cannabigerovarin)
  • CBGVA (Cannabigerovarinic acid)
  • CBL (cannabicyclol)
  • CBN (cannabinol)
  • CBT (cannabicitran)
  • CBV (cannabivarin)
  • CP-55940 – synthetic cannabinoid
  • Dimethylheptylpyran – synthetic cannabinoid
  • Dronabinol (also known as Marinol) – synthetic cannabinoid
  • HU-210 – synthetic cannabinoid
  • HU-331 – synthetic cannabinoid
  • JWH-018 – synthetic cannabinoid
  • JWH-073 – synthetic cannabinoid
  • JWH-133 – synthetic cannabinoid
  • Levonantradol (also known as Nantrodolum) – synthetic cannabinoid
  • Nabilone (also known as Cesamet, Canemes)- synthetic cannabinoid
  • SR144528 – synthetic cannabinoid
  • THC (Δ9–tetrahydrocannabinol)
  • THCA (tetrahydrocannabinolic acid)
  • THCA (Δ9-tetrahydrocannabinolic acid)
  • THCV (tetrahydrocannabivarin)
  • THCVA (Tetrahydrocanabivarinic acid)
  • WIN 55,212-2 – synthetic cannabinoid

The last few years have seen a marked increase in the marketing and use of CBD as an alternative to anti-depression medication. This is due to changes in US federal and state laws that have allowed for the resumption of the production of hemp in the US as well as states that have allowed the use of cannabis for medical and recreational purposes.

What is CBD?

Cannabidiol, also known as CBD, is a chemical compound found in both cannabis plants and in humans. CBD is a non-intoxicating psychoactive chemical that’s been found to help in a number of processes in the body. This is due to the numerous properties that CBD possesses. CBD has been found to be a natural:

  • Analgesic
  • Anti-anxiety
  • Antibacterial
  • Antidepressant
  • Antifungal
  • Anti-inflammatory
  • Anti-psychotic
  • Neuroprotective

CBD is derived from all 3 species of cannabis plants. These are:

  • Cannabis Sativa (Sativa) – This is a cannabis species with low THC content (less than 0.3%) and higher CBD content. This is this the traditional species that’s been known as hemp. Sativa is known as one of the most versatile plants in the world and can be used for a number of things including food, clothing, medicine, building supplies, paper, and as a way to fight erosion along rivers.
  • Cannabis Indica (Indica) – Indica is the plant traditionally associated with marijuana. The THC content in these plants can range from 5% to 35%. Indica was originally indigenous to India and in addition to marijuana, it is used in the hashish. Hashish is the resin made from cannabis.
  • Cannabis Ruderalis (Ruderalis) – Ruderalis is known as Russian hemp. Ruderalis has the lowest THC content of the 3 species of cannabis, usually less than 0.1%. It’s usually used to crossbreed with Sativa or Indica due to its auto-flowering feature that allows for faster harvesting. On its own, it usually is used for medicine or food but due to its short stature has limited use.

In the US, Sativa is the crop of choice to derive CBD from as federal laws prohibit the production of cannabis products with more than 0.3% THC.

THC is the psychoactive intoxicant in marijuana that causes a user to get high when consumed or smoked.

In addition to depression, CBD has been studied for over 2 decades and has been found to be effective in treating well over 100 conditions and their related symptoms. These include:

How CBD Affects Moods

CBD is used to treat a number of conditions that are associated with depression including bipolar disorder, anxiety, post-traumatic stress disorder (PTSD), and a host of other conditions.

This is due to the many health benefits that CBD has been proven to have. One of the more promising of these benefits for people suffering from depression is the neuroprotective properties of CBD.

In the case of depression and depression-related conditions, CBD can reduce and even stamp out the symptoms of depression.

This is because CBD works with neuroreceptors in the body that naturally process cannabinoids. This system of neuroreceptors is called the endocannabinoid system or ECS.

The ECS is comprised of neurotransmitters that bind to cannabinoid receptors and cannabinoid receptor proteins that are located in the brain and throughout the central nervous system and peripheral nervous system.

The ECS is involved in regulating physiological and cognitive processes such as:

  • appetite
  • fertility
  • mediating the pharmacological effects of cannabis
  • memory
  • mood
  • pain-sensation
  • postnatal development
  • pregnancy
  • prenatal development

Two main receptors in the ECS have been discovered: CB1 or cannabinoid or cannabinoid receptor type 1 and CB2 or cannabinoid receptor type 1. CB1 receptors are mostly found in the brain and nervous systems as well as in peripheral organs and tissues. They are the main molecular target of the endocannabinoid binding molecule, anandamide, and THC. The other main endocannabinoid is arachidonoylglycerol (2-AG) which is works with both CB1 and CB2, along with CBD. 2-AG and CBD are involved in the regulation of appetite, immune system functions, mood modulation, and pain management.

One of the keys to helping people suffering from depression is regulating the levels of serotonin in the body. Serotonin is a neurotransmitter that transmits messages between nerve cells, it’s active in constricting smooth muscles, contributes to wellbeing and affects “happiness”. It works in concert with melatonin to regulate the body’s sleep-wake cycles and the internal clock. Serotonin plays a role in appetite, emotions, motor, cognitive, and autonomic functions.

A study that was published in 2016 looked at that effects of serotonin levels in mice when CBD was introduced. Researchers found that CBD worked fasted and lasted longer than traditional synthetic medications that are usually prescribed for depression. The study concluded that “Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signaling through a 5-HT1A receptor-dependent mechanism.”  (https://www.ncbi.nlm.nih.gov/pubmed/26711860)

Another study in 2016 found that “Systemic administration of cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects. The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation. The brain regions involved in CBD-induced antidepressant-like effects remain unknown. The ventral medial prefrontal cortex (vmPFC), which includes the infralimbic (IL) and prelimbic (PL) subregions, receives dense serotonergic innervation and plays a significant role in stress responses.” It further concluded that “administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors.” (https://www.ncbi.nlm.nih.gov/pubmed/26801828)

A study published in early 2019 looked closer at how fast CBD worked to help those suffering from depression. This study found that “Results showed that a single dose of CBD dose-dependently induced antidepressant-like effect (7-30 mg/kg) in Swiss mice submitted to the forced swim test (FST), 30 min (acute) or 7 days (sustained) following treatment. Similar effects were observed in the Flinders Sensitive and Flinders Resistant Line (FSL/FRL) rats and the learned helplessness (LH) paradigm using Wistar rats.” It concluded that “These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway. The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.” (https://www.ncbi.nlm.nih.gov/pubmed/29869197)

Traditional Depression Treatments

Traditional treatment for depression includes individual and/or group therapy, usually cognitive behavioral therapy (CBT). CBT works by helping patients explore and change negative distorted thoughts, beliefs, attitudes, and behaviors to improve emotional wellness.

CBT is usually provided in combination with a regimen of antidepressant medications. Doctors have a wide selection of medications to prescribe and each belongs to one of several classes of drugs that act in different manners on the brain. While many generally provide similar results, the effects can vary from person to person and they each have side effects.

Selective Serotonin Reuptake Inhibitors (SSRI)

Among the more common types of antidepressants are SSRIs. These are popular because the likelihood of addiction to them is extremely low, so they can be taken for long periods of time.

SSRIs block cells in the brain from reabsorbing serotonin. This leaves more serotonin available for the sending of nerve impulses. A person taking an SSRI will experience an improvement of mood due to the increased serotonin levels, which decrease the bouts of depression.

SRIs, while they can be effective, are designed to be prescribed for no longer than 12 months. After this time they’ll usually become ineffective, so doctors often have to change the prescription to another SSRI or another class of medications. Common SSRIs include:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Prozac (fluoxetine)
  • Luvox (fluvoxamine)
  • Paxil (paroxetine)
  • Pexeva (paroxetine)
  • Zoloft (sertraline)

Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)

The second most common type of antidepressant prescribed is SNRIs. In addition to affecting serotonin levels, SNRIs also help manage levels of norepinephrine. Norepinephrine is the substance that sends signals to the brain and body to perform actions. It affects anxiety, alertness, glucose production, blood pressure, among others. The most common SNRIs prescribed are Effexor XR (venlafaxine) and Cymbalta (duloxetine).

Monoamine Oxidase Inhibitors (MAOI)

MAOIs have been prescribed since the 1950s. These are among the most powerful antidepressants and are prescribed now for the most severe cases. MAOIs inhibit the activity of one or both of the enzymes monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B), both of which regulate different neurotransmitters in the brain.

This class of medications has many bad interactions with other medications, illicit drugs, and alcohol, so patients who use these may not be suitable for this class of medication.

Among the more common MAOIs are:

  • Emsam (selegiline)
  • Marplan (isocarboxazid)
  • Nardil (phenelzine)
  • Parnate (tranylcypromine)

Tricyclic Antidepressants (TCA)

One of the original classes of antidepressants is TCAs. Discovered in the 1950s, TCA prescriptions have decreased in recent years in favor of SSRIs and SNRIs. While not the go-to drug of choice anymore for physicians to prescribe for depression, doctors tend to look towards TCAs when SSRIs and SNRIs fail to work for the patient. TCAs work similarly to SNRIs as they also reduce the brain’s absorption of serotonin and norepinephrine into the brain. Many doctors are hesitant to prescribe TCAs due to the many side effects and the propensity for addiction. Among the most common TCAs are:

  • Elavil (amitriptyline)
  • Pamelor (nortriptyline)
  • Tofranil (imipramine)

Side Effects

Among the many reasons that CBD is being looked at to supplement or even replace many antidepressants is the side effects. The classes of medications listed have a slew of side effects that can include:

  • addiction
  • blurry vision
  • constipation
  • diarrhea
  • difficulty urinating
  • dizziness
  • drowsiness
  • dry mouth
  • fatigue
  • feeling agitated or restless
  • headaches
  • increased appetite
  • increased blood pressure
  • lightheadedness
  • loss of appetite
  • low blood pressure
  • nausea
  • profuse sweating
  • sexual dysfunction
  • sleep problems
  • tremors
  • upset stomach
  • weight gain
  • weight loss

CBD, on the other hand, has very few side effects. These include a feeling of drowsiness and dry mouth. CBD isn’t addictive, can work well with other medications, and isn’t dangerous over the long term.


Clinical studies, as well as history, tells us that CBD and cannabis can be effective in treating depression. The difference between now and the ancient use of cannabis is that we now have the medical and scientific knowledge to determine how CBD and other cannabinoids affect the brain to achieve the antidepressant effects.

And while more research needs to be done, all signs point to CBD eventually becoming the tool of choice to fight depression. The lack of side effects, the wide availability, and the fact that the body is a natural producer and processor of CBD make it a prime candidate to overtake all other medications on the market in the fight against depression.