Anxiety is one of the most common and impairing mental disorders, affecting around 29% of the U.S population [1]. However, current pharmaceutical treatments remain problematic with low recovery rates, poor tolerability and adherence problems [2].

A growing body of research shows that cannabidiol (CBD) oil, a non-psychoactive constituent of cannabis, may be an effective alternative to traditional anti-anxiety medications [3] [4].

cbd vs xanax zoloft ssri for anxiety

What is Anxiety?

Anxiety is the body’s adaptive response to fear. Common symptoms include:

  • Sweaty palms
  • Racing heart
  • Rapid breathing
  • Trembling
  • ‘Butterflies’ in your stomach
  • Hyper-vigilance
  • A burst of adrenaline

When faced with a stressful or threatening situation, a certain level of anxiety is both normal and essential. In fact, anxiety evolved to keep us safe when under threat. For example, imagine you’re doing some gardening, and as you’re about to pull out a weed, you see a snake. Suddenly, your heart is racing, and an immediate burst of adrenaline compels you to jump towards safety.

Anxiety is also intended to motivate us. If you have an upcoming exam, a certain level of anxiety can help you prepare better. Likewise, feeling anxious before a competitive match can lead to improved athletic performance. However, in these situations, the anxiety resolves once the ‘stressor’ is removed.

CBD for anxiety

What is an Anxiety Disorder?

Anxiety disorder occurs when anxiety doesn’t go away—and begins to severely impact a person’s day-to-day life. While it’s normal to feel anxious when faced with a real threat (e.g. a snake), someone with an anxiety disorder will have the same response to a perceived threat (e.g. getting their haircut or meeting a new person).

In medical terms, anxiety disorder is defined as a psychological and physiological state of excessive or persistent fear brought on by a perceived threat. It’s characterized by intense feelings of worry that are difficult to control.

There are several different types of anxiety-related disorders:

  • Obsessive-compulsive disorder (OCD)
  • Post-traumatic stress disorder (PTSD)
  • Generalized anxiety disorder (GAD)
  • Social anxiety disorder (SAD)
  • Panic disorder (PD)

What is Cannabidiol (CBD) oil?

Cannabidiol (CBD) oil is extracted from the industrial hemp and marijuana plant, collectively called Cannabis sativa. There are 85 naturally-occurring cannabinoid compounds in cannabis and CBD is the second most abundant, after tetrahydrocannabinol (THC). THC is widely known for its psychoactive properties, while CBD, even at high doses, lacks these mind-altering effects.

CBD has not only received attention for its anti-anxiety effects but also its broad therapeutic benefits, including anti-psychotic, anti-inflammatory, analgesic, and neuroprotective [5].

Is CBD Effective for Anxiety?

CBD was first isolated in 1940.

However, it wasn’t until the 21st century that researchers discovered its anti-anxiety properties. A prominent study compared the effects of a simulated public speaking test on patients with Generalized Social Anxiety Disorder (SAD). Pre-treatment with a single dose of CBD significantly reduced symptoms of anxiety (e.g. increased heart rate, blood pressure, and flushing of the skin) in SAD patients, but also decreased cognitive impairment and speech discomfort, compared to the placebo group. Interestingly, negative self-statements were also near abolished by the CBD [6].

The anti-anxiety effects of CBD have also been demonstrated in animal studies.

CBD decreases anxiety in rats subjected to elevated maze tests [7], Vogel stress (water deprivation and punishment) tests [8], and contextual conditioned fear tests (footshocks) [9]. CBD is also shown to increase social interaction between rodents [10].


Does CBD Have Side Effects?

A 2011 review [11], which examined the safety and side effects of CBD in various concentrations, reported that CBD oil:

  • does not alter psychomotor and psychological functions
  • does not affect heart rate, blood pressure, or body temperature (does up to 600 mg)
  • does not impact digestion or cause changes in food intake/appetite
  • does not cause catalepsy (trance-like state marked by loss of limb control)

According to the review, chronic CBD use and high doses up to 1,500 mg/day are well tolerated in humans [11]. On the contrary, some animal and in vitro studies suggest CBD may inhibit the hepatic drugs and drug transporters, reduce receptor activity and decrease fertility. Although more research is required, an in vitro test on animals showed that CBD does not significantly alter embryonic development at low concentrations [12].

A more recent 2015 review, found the most commonly reported side effects of CBD use are diarrhea, tiredness, and changes in weight [13]. However, the review also concluded that CBD has less unfavorable side effects than other medications used to treat anxiety.

A 2015 study on #CBD concluded that CBD has less favorable side effects than other medications used to treat #anxiety. 

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With that said there are certainly still areas of concern that require further research. Cannabinoids also exert an inhibitory response on the immune system, including decreasing the production of important immune cells, which could worsen disease progression, increase tumor growth and exacerbate allergic inflammation [14].

Furthermore, if CBD is administered before THC, CBD can increase the potency of THC by rapidly increasing absorption [11]. It must also be noted that regular cannabis use can cause adverse effects, including anxiety.


How Does CBD Impact the Brain and Body?

CBD has a multifold impact on the human body and brain.

The Endogenous Cannabinoid System

CBD appears to modulate emotional responses through the endogenous cannabinoid (eCB) system. The eCB system consists of two different cannabinoid receptors: CB1 and CB2.

CB1 receptors are located primarily in the brain within regions responsible for emotional processing, such as the amygdala, hippocampus, and cerebral cortex. In contrast, CB2 receptors are predominantly located within immune cells, whilst also being present in the brain.

Both cannabinoid receptors regulate the release of neurotransmitters. Neurotransmitters are chemical messengers that communicate with (to either excite or inhibit) nerve cells throughout the body. In the presence of CBD, CB1 receptors inhibit neurotransmitter release, which prevents excessive stimulation of the nervous system, thus decreasing anxiety. CBD appears to have a mild effect on the CB2 receptors, by mediating the release of cytokines from immune cells in a manner that helps to reduce inflammation and pain.

It is also believed CBD has an indirect effect on cannabinoid receptors (primarily CB1) by inhibiting the enzymatic breakdown of anandamide [15]. Anandamide is an endogenous ligand produced naturally by the body that binds to CB1 receptors and further regulates the release of neurotransmitters [16]. It is known as the body’s natural “anti-anxiety” molecule, aptly named after Ananda, the Sanskrit word for “joy, bliss, or happiness.” CBD allows anandamide to stay in the system longer and exert a sustained calming effect.

Serotonin Type 1A Receptors

The neurotransmitter, serotonin, is well-known for its mood-boosting effects on the brain. High concentrations of CBD may decrease symptoms of anxiety by exerting similar effects to serotonin [17]. While the exact mechanism remains unclear, it is proposed that CBD directly activates serotonin type 1A (5-HT1A) receptors within specific “defense” areas of the brain enabling users to better mediate their stress response.

Regulates Cerebral Blood Flow

Recent neuroimaging studies show that CBD alters activity levels within the emotional control centers of the brain [18]. In particular, CBD reduces blood flow to the amygdala, as well as the anterior and posterior cingulate cortex in patients presented with fearful facial cues [19]. Another more recent study demonstrated that CBD inhibits over-stimulation of areas responsible for decision making, impulse control, and emotional processing [20].

Alternative Options for Anxiety: Xanax & Zoloft

Mainstay pharmacological treatments for anxiety belong to two different classes: benzodiazepines (BZD) and selective serotonin reuptake inhibitors (SSRI). BZDs are among the most widely prescribed anti-anxiety medications within the United States, with up to 1 in 4 patients with anxiety using a form of BZD [21].

CBD Oil vs Xanax for Anxiety

Xanax is the trade name for alprazolam, a high-potency benzodiazepine (BZD) prescribed for the short-term management of anxiety and insomnia. Clinical studies demonstrate that Xanax (alprazolam) reduces the frequency of panic attacks and the severity of generalized anxiety disorder [22] [23].

Approved by the FDA in 1981, the drug works by enhancing the effects of a neurotransmitter, gamma-aminobutyric acid (GABA). Following either oral or inhaled administration, Xanax binds with GABA alpha type 1 receptors to cause a general slowing of brain activity (sedation) as well as GABA alpha type 2 receptors to decrease anxiety [24]. It is believed the GABA system alters the release for neurotransmitters, such as serotonin and noradrenaline. However, the exact mechanisms are unknown.

Xanax can provide relief within 15 minutes of oral administration, with peak plasma concentration seen within 1 to 2 hours, which is a relatively faster onset than other anti-anxiety medications, like SSRIs [25]. The onset for CBD oil, on the other time, is generally rapid, but varies significantly depending on the administration. Taken orally, peak plasma concentrations are seen within 3 hours, whereas when inhaled, effects are felt within as little as 10-15 minutes [26].

Common Side Effects of Xanax

Xanax has several serious side effects, including:

  • sedation
  • cognitive impairment and slow reaction times
  • Amnesia (temporary memory loss)
  • Ataxia (decreased balance and coordination)
  • confusion
  • drowsiness
  • muscle weakness
  • aggressive behavior [31] (however, can reduce agitation in those with dementia)
  • Increased risk of drug abuse

As Xanax depresses the central nervous system, it can affect cognitive function and driving skills [32]. Do not operate heavy machinery or drive a car until you know how Xanax affects you. CBD oil, on the other hand, has been shown to improve cognition and exert neuroprotective factors [33] [34].


CBD Oil vs Xanax Addiction

In general, Xanax has a good record of safety. However, there is a high risk of low-dose dependency, even after just one week of continuous treatment, as well as serious drug abuse problems [27]. In contrast, “CBD exhibits no effects indicative of any abuse or dependence potential,” according to the World Health Organisation (WHO) [26].

World Health Organization: “CBD exhibits no effects indicative of any abuse or dependence potential”

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BZDs, like Xanax, are abused most commonly in combination with opioids and alcohol to produce a high [28]. Worryingly, overdoses are common as many patients are unaware of the drug’s potency, which is 10 times stronger than that of diazepam, another benzodiazepine. According to the National Institute of Drug Abuse, the number of deaths from Benzodiazepine overdose has soared in recent years, with an 8-fold increase since 2002 [29].

Furthermore, discontinuation of Xanax is associated with severe withdrawal and rebound symptoms, including seizures, particularly at doses greater than 4 mg/day [30]. Therefore, discontinuation must be tapered. Conversely, no withdrawal or rebound symptoms have been reported with CBD oil. In fact, CBD can be effective for the treatment of cannabis withdrawal symptoms [39].

CBD Oil vs Xanax: Interactions and Precautions

Xanax can induce potentially life-threatening interactions with other drugs, including opioids and other central nervous system depressants. For a full list of interactions and contraindications see here.

Xanax should not be used during pregnancy due to its sedative effect, which can cause serious harm to an unborn baby, including congenital abnormalities. While there is a lack of conclusive data, CBD oil is also not recommended during pregnancy. However, some women have reported using it to reduce pregnancy-related nausea.

CBD Oil vs Zoloft for Anxiety

Zoloft is the trade name for sertraline, an antidepressant medication. It belongs to a class of medications known as selective serotonin reuptake inhibitors (SSRI). These medications work by preventing the reabsorption of serotonin in the brain after it’s released. Serotonin is a neurotransmitter that plays an important role in regulating mood. Once it builds up, it can help users feel more positive. However, unlike CBD oil, it can take weeks to months for SSRI’s to take effect.

Zoloft is approved by the FDA to treat major depressive disorders (MDD) and premenstrual dysphoric disorder (PMDD), as well as posttraumatic stress disorder (PTSD), social anxiety disorder (SAD), and panic disorder. It is also approved to treat obsessive-compulsive disorder (OCD) but has not been approved for generalized anxiety disorder (GAD) or bipolar disorder.

Common Side Effects of Zoloft

  • drowsiness
  • diarrhea
  • nausea
  • tremor
  • decreased appetite
  • dry mouth
  • sweating
  • Insomnia
  • Nervousness, agitation or restlessness
  • blurred vision
  • sexual side effects (reduced libido, erectile dysfunction)

Severe Side Effects of Zoloft 

Although antidepressants are generally considered beneficial in the treatment of anxiety and depression, selective serotonin reuptake inhibitors (SSRI), like Zoloft, may cause the emergence or aggravation of suicidal thoughts in vulnerable individuals [35]. A 2017 review recently warned that children, adolescents, and adults under 25 are at high risk of severe adverse side effects and suicidal ideation [36].

Zoloft, and other SSRIs, including Prozac, increase the risk of serotonin syndrome, a potentially life-threatening adverse drug reaction characterized by excessive serotonin [37]. Symptoms of serotonin syndrome range from a barely noticeable tremor to serious disturbances in mental ability, neuromuscular rigidity, and hyperthermia in lethal cases. CBD oil and SSRIs have completely different mechanisms of action. CDB does not directly influence levels of serotonin in the brain, therefore is not associated with this condition.

Zoloft also increases the risk of seizures in patients with a seizure disorder, such as epilepsy. Seizures are also common when the medication is stopped abruptly. Conversely, several clinical trials have indicated that CBD oil is an effective treatment for epilepsy [26].

CBD Oil and Zoloft Interactions

While both CBD oil and Zoloft are well-tolerated with a good safety profile, they can interact with other medications causing adverse reactions. However, much more is known about the interactions of Zoloft. For example, Zoloft can cause adverse reactions when used in combination with monoamine oxidase inhibitors (MAOIs), pimozide, disulfiram, phentermine, and methadone. SSRIs also present an increased risk of bleeding, especially when used in combination with non-steroidal anti-inflammatories (NSAIDs) and anticoagulant drugs such as aspirin and warfarin. For a full list of interactions and contraindications see here.

CBD Oil and SSRI Potential for Dependence

A growing body of evidence, mainly case studies, suggests that there is potential for the misuse and abuse of SSRIs, especially since these drugs reportedly cause a stimulant effect at high doses [38]. This is not the case with CBD. Pure CBD oil does not increase the release of dopamine, unlike SSRIs, and according to well-controlled human experiments, is not associated with abuse potential or dependence [26].

CBD Oil is Generally Considered a Safe Alternative

Studies have indicated that CBD can have positive impacts on anxiety when compared to both pharmaceutical benzodiazepines (BZD) and selective serotonin reuptake inhibitors (SSRI). Pure CBD oil appears to have fewer adverse side effects with a potentially lower risk of addiction and toxicity. However, the CBD industry is still largely unregulated and continuously evolving. 


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