cbd and celexa

Cbd and celexa

Many drugs are broken down by enzymes in the liver, and CBD may compete for or interfere with these enzymes, leading to too much or not enough of the drug in the body, called altered concentration. The altered concentration, in turn, may lead to the medication not working, or an increased risk of side effects. Such drug interactions are usually hard to predict but can cause unpleasant and sometimes serious problems.

CBD has the potential to interact with many other products, including over-the-counter medications, herbal products, and prescription medications. Some medications should never be taken with CBD; the use of other medications may need to be modified or reduced to prevent serious issues. The consequences of drug interactions also depend on many other factors, including the dose of CBD, the dose of another medication, and a person’s underlying health condition. Older adults are more susceptible to drug interactions because they often take multiple medications, and because of age-related physiological changes that affect how our bodies process medications.

Doubling up on side effects

Absolutely. Inhaled CBD gets into the blood the fastest, reaching high concentration within 30 minutes and increasing the risk of acute side effects. Edibles require longer time to absorb and are less likely to produce a high concentration peak, although they may eventually reach high enough levels to cause an issue or interact with other medications. Topical formulations, such as creams and lotions, may not absorb and get into the blood in sufficient amount to interact with other medications, although there is very little information on how much of CBD gets into the blood eventually. All of this is further complicated by the fact that none of these products are regulated or checked for purity, concentration, or safety.

Does the form of CBD matter?

While generally considered safe, CBD may cause drowsiness, lightheadedness, nausea, diarrhea, dry mouth, and, in rare instances, damage to the liver. Taking CBD with other medications that have similar side effects may increase the risk of unwanted symptoms or toxicity. In other words, taking CBD at the same time with OTC or prescription medications and substances that cause sleepiness, such as opioids, benzodiazepines (such as Xanax or Ativan), antipsychotics, antidepressants, antihistamines (such as Benadryl), or alcohol may lead to increased sleepiness, fatigue, and possibly accidental falls and accidents when driving. Increased sedation and tiredness may also happen when using certain herbal supplements, such as kava, melatonin, and St. John’s wort. Taking CBD with stimulants (such as Adderall) may lead to decreased appetite, while taking it with the diabetes drug metformin or certain heartburn drugs (such as Prilosec) may increase the risk of diarrhea.

Cbd and celexa

We previously reported that CBD treatment increased the expression of generalized fear in male mice (Uhernik et al. 2018). In contrast, generalized fear was reduced by CBD and citalopram in this study. This suggested that, like with contextual memory, a sexual dimorphism is present in the effects of CBD on generalized fear memory. Additionally, both drugs significantly decreased the level of generalized fear measured on the fourth day of extinction training relative to control; however, citalopram-treated mice did not show a significant level of extinction when assessed by comparing freezing levels across the 5 days of experimentation (Fig. 4b). This was apparently due to the large reduction in the size of the original freezing response measured as the baseline for extinction 24 h after conditioning. Therefore, the apparent extinction effect of citalopram, and to an extent CBD (which had a similar large effect on the original memory), could be mostly attributable to an inhibition of fear generalization to the novel context, as assessed 24 h after conditioning, and less so to a direct enhancing effect on extinction learning.

Fear memory extinction training was conducted at 24-h intervals for 4 days following the first day of memory testing. It was completed by first exposing mice to the novel context for a 3-min baseline period, followed by seven 30 s presentations of the auditory cue which were spaced at 120 s intervals. In this period, we assessed generalized fear, and auditory cue-associated memory, respectively. Four hours after that, mice were returned to the original context for 5 min to assess contextual memory strength.

For extinction of auditory-cued memory, regardless of treatment, all three groups of mice showed significantly decreased freezing to the auditory cue by the fourth day of extinction training when analyzed within treatment groups across the 5-day period. However, the level of freezing was significantly reduced in both CBD and citalopram treated mice when compared across treatment groups within the final day of extinction training (Fig. 4a). This result shows that extinction learning was present for all groups, and that both CBD and citalopram were able to significantly enhance extinction learning for this memory type, when administered one-time prior to trace-fear conditioning. Notably, the difference in final levels of freezing was not significantly different between the CBD and citalopram treated mice.

All fear conditioning was completed in context A, 24 h after habituation, and on the second day of experimentation. Each of the three conditioning groups was further divided into three treatment groups, vehicle, CBD, or CIT. Mice in the vehicle or CBD groups received an IP injection 30 min prior to conditioning whereas those mice that received CIT were injected 60 min prior to fear conditioning. This resulted in a final total of nine experimental groups containing 12 animals per group. Paired conditioning consisted of a 2 min baseline period followed by seven 30-s long presentations of the CS each paired with an US. A trace interval of 17 s was placed between presentations of the CS and US, and the seven CS-US pairs were separated by an inter-trial interval (ITI) of 2 min. Animals in the unpaired groups received seven presentations of the US at pseudo-random intervals. Non-conditioned animals received seven presentations of the CS with a 2-min ITI. All animals were exposed to the conditioning chamber for the same overall duration regardless of the conditioning group.

Auditory-cued fear memory appeared similar after 24 h but was more easily extinguished with CBD or citalopram

Results of extinction training over a four day period following the original memory test in female mice. a. Extinction of the tone-associated memory was assessed in the novel context by recording freezing levels averaged across seven presentations of the auditory cue and comparing these levels within groups across days, and across treatment groups on the last day, with a t-test (*p = < 0.05). b.Contextual memory extinction was similarly assessed by averaging freezing levels over a five minute period in the original conditioning context (*p < 0.05). c. Extinction of generalized fear was similarly assessed by measuring freezing levels during a three minute baseline period in the novel context (*p < 0.05). The timeline for the experiment is shown in the inset above

Finally, generalized fear memory was significantly extinguished over the 4 day period of extinction training in both vehicle controls and CBD-treated mice, but not in the citalopram-treated group. Therefore, citalopram-treated animals did not show extinction of generalized fear with our protocol. This was likely a result of the greatly reduced original memory; however, this was also true for the CBD-treated animals which, despite a similar reduction in the memory measured 24 h post-conditioning, did show extinction of the memory (Fig. 4c). In addition, on the final day of extinction training, both CBD- and citalopram-treated mice showed significantly lower levels of freezing in comparison to control (p = 0.005 and 0.04, respectively). Therefore, both CBD- and citalopram-treated animals showed reduced levels of fear generalization across the entire experimental period, however, the generalized fear memory was extinguished only in the CBD-, but not the citalopram-treated animals.

Consistent with our previous study using male mice, a single pre-acquisition dose of CBD to females did not affect auditory cue-associated memory recall when assessed 24 h after trace fear conditioning (Fig. 1) (Uhernik et al. 2018). We saw the same lack of effect using citalopram in this study; however, this is contrary to reports showing an increase in auditory-cued fear following delay conditioning when citalopram was administered with the same timing to male rats (Burghardt et al. 2004; Inoue et al. 1996). This difference could be attributed to differences in processing memories formed with trace versus delay conditioning, the use of rats instead of mice, or to sex differences (Jurkus et al. 2016).

Results

All mice were divided into three conditioning groups: paired conditioned, unpaired conditioned, and non-conditioned. All mice, regardless of conditioning group, were individually placed in the fear conditioning chamber, configured in context A, and habituated for 20 min before being returned to their home cages. During habituation, mice in the unpaired group received seven 30 s presentations of the conditioning stimulus. Non-conditioned and paired conditioned mice did not receive tone presentations during the habituation period; however, these mice were habituated for the same duration of time as the unpaired group.

Auditory-cued trace fear conditioning was conducted shortly after dosing female C57BL/6 mice, with either CBD or citalopram (10 mg/kg each), by pairing auditory tones with mild foot shocks. Auditory-cued, contextual, and generalized fear memory was assessed by measuring freezing responses, with an automated fear conditioning system, 24 h after conditioning. Each memory type was then evaluated every 24 h, over a 4-day period in total, to create an extinction profile. Freezing outcomes were statistically compared by ANOVA with Tukey HSD post hoc analysis, N = 12 mice per experimental group. Evaluation of sexual dimorphism was by comparison to historical data from male mice.