Commercial antidepressants typically take two to four weeks to have a significant effect on a depressed patient.
They are also ineffective in many cases. Finding new drugs for depression that are fast-acting and have more lasting effects is the goal of research conducted by Brazilian scientists in São Paulo State in collaboration with Danish colleagues.
Their study found that a single dose of cannabidiol in rats with symptoms of depression was highly effective, eliminating the symptoms on the same day and maintaining the beneficial effects for a week.
The findings reinforce those of prior research showing that cannabidiol, a component of Cannabis sativa, the plant most commonly used to make marijuana, has promising therapeutic potential in the treatment of broad-spectrum depression in preclinical and human models.
The results have been published in an article in the journal Molecular Neurobiology by researchers of the group led by Sâmia Regiane Lourenço Joca, a professor in the University of São Paulo’s Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP) in Brazil.
The first author is Amanda Juliana Sales, who has a PhD scholarship from FAPESP. The research itself was supported by FAPESP via a Thematic Project, by Brazil’s National Council for Scientific and Technological Development (CNPq), and by Denmark’s Aarhus University Research Foundation.
The research on cannabidiol is being performed in collaboration with a group led by Francisco Silveira Guimarães, a professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP). Gregers Wegener, a professor in Aarhus University’s Department of Clinical Medicine, is also collaborating.
“Brazil has pioneered the study of cannabidiol. Today is very different from 30 years ago, when we began studying the substance and faced prejudice because of the association with marijuana,” Guimarães told Agência FAPESP.
Although cannabidiol is extracted from the marijuana plant, Guimarães stressed that it produces neither dependence nor psychotropic effects. “The main psychoactive component of marijuana is tetrahydrocannabinol, known as THC. Cannabidiol, on the contrary, blocks some of the effects of THC,” he said.
Scientists are investigating the effects of cannabidiol in search of drugs with shorter latency and hence the capacity to be faster-acting than conventional antidepressants.
According to Guimarães, the available antidepressants obtain results in approximately 60% of patients. The rest receive inadequate treatment even after trying various different options for several months. “This evidences the need to find new drugs with better therapeutic potential,” she said.
The researchers used rat and mouse lines selected by cross-breeding to develop symptoms of depression. The tests and behavioral analysis involved a total of 367 animals.
Five tests were performed altogether. “We submitted the animals to situations of stress such as the forced swimming test,” said Joca, who is also a visiting professor at Aarhus University.
Before the test, some of the animals were given an injection of cannabidiol with doses of 7, 10 and 30 mg/kg in saline solution, and the rest, which were the control group, received only saline.
After 30 minutes, the animals were placed for five minutes in cylinders with a height of 25 cm and a diameter of 17 cm, containing 10 cm of water for mice and 30 cm of water for rats.
“The water depth is calculated to force them to swim by preventing them from touching the bottom with their feet or tails. They learn to float after swimming for a short time. They remain practically immobile while floating, merely keeping their heads above water to avoid drowning. This floating behavior, when they stop swimming, is classified as immobility,” Joca said.
“The forced swim test is used to measure the effect of antidepressant drugs because all known antidepressants shorten the duration of immobility and hence lengthen swim time. A reduction in immobility time in this test is interpreted as ‘antidepressant-like’ behavior.”
The researchers found that cannabidiol induced acute and sustained antidepressant-like effects in mice submitted to the forced swim test.
“However, to make sure this result isn’t due to the increase in movement caused by a psychostimulant effect leading the animals to swim more vigorously, for example, we performed a separate test to control for locomotor activity,” Joca explained.
“To do this we used the open-field test, which consists of putting the animal in a novel arena and letting it explore the new environment freely while its locomotor and exploratory activity is recorded. A drug is said to have potential antidepressant effects if it reduces immobility time and increases swim time in the forced swim test without increasing locomotor activity in the open-field test, showing that the effects observed in the forced swim test aren’t secondary to nonspecific alterations in locomotor activity.”
Restoration of neuronal circuitry
The conclusion was that the effects of treatment with cannabidiol were fast-acting and sustained, persisting for up to seven days after a single dose was administered to animals belonging to different models of depression (including a stress model and a genetic susceptibility model).
The findings were reproduced in three different sets of animals at the laboratories of FCFRP-USP, FMRP-USP and Aarhus University.
“When we studied the mechanisms involved in these effects, we found that treatment with cannabidiol induces a rapid rise in levels of brain-derived neurotrophic factor, or BDNF, a neurotrophin that plays a key role in neuronal survival and neurogenesis, the formation of new neurons in the brain,” Joca said. “We also observed an increase in synaptogenesis in the prefrontal cortex of these animals.” Synaptogenesis is the formation of synapses between neurons in the central nervous system.
Seven days after treatment, the researchers observed a rise in the number of synaptic proteins in the prefrontal cortex, which is closely linked to depression in humans. “In light of this finding, we believe cannabidiol rapidly triggers neuroplastic mechanisms that help repair the neuronal circuitry that gets damaged in depression,” Joca said.
The beneficial action of cannabidiol is not limited to the prefrontal cortex, however. “In a separate study, we showed that the effects of cannabidiol also involve neuroplastic mechanisms in the hippocampus, another structure involved in the neurobiology of depression,” she noted.
According to Joca, if studies in humans also find cannabidiol to be beneficial in treating depression, given that cannabidiol is already used in humans to treat other diseases or disorders, “they could result in an important advance in the treatment of depression, potentially helping patients who suffer for weeks, often with a risk of suicide, until the treatment starts working.”
Studies in humans
The researchers are currently investigating other mechanisms involved in the effects of cannabidiol, as well as its efficacy in animal models of resistance to conventional treatment.
“For example, we’re studying whether cannabidiol would also be effective in patients who don’t respond to conventional therapy and whether combining it with antidepressants would improve their symptoms. Indeed, we’ve just published another paper in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry, showing that treatment with cannabidiol facilitates serotonergic neurotransmission in the central nervous system and that combining it with low doses of selective serotonin reuptake inhibitor antidepressant drugs, or SSRIs, such as fluoxetine induces a significant antidepressant effect,” Joca said.
“So there’s a possibility that combining cannabidiol with SSRIs might allow the latter to be used in lower doses, perhaps reducing their adverse side-effects while maintaining the therapeutic effect of higher doses.”
According to the authors, therefore, cannabidiol may not only be a faster-acting antidepressant than conventional drugs but also improve the response to such drugs when taken in combination with them.
“Our evidence suggests these effects occur by inducing neuroplastic alterations in the prefrontal cortex and hippocampus, which are brain structures involved in the development of depression. Because cannabidiol is used in humans to treat other conditions, we believe it can also be studied in humans for the treatment of depression in the near future,” Joca said.
The Latest on: Depression
via Google News
The Latest on: Depression
- The Depression-era green program regaining tractionon June 25, 2020 at 7:07 am
Momentum on Capitol Hill is growing for a conservation program based on the Great Depression-era Civilian Conservation Corps as a way to put millions of young people to work while also restoring the ...
- Percentage of Americans who say economy is in a recession or depression drops sharply: Gallupon June 25, 2020 at 6:59 am
The percentage of Americans who say they think the economy is in a recession or depression has dropped sharply from May as the economy slowly makes up ground lost during the coronavirus pandemic.
- ‘Depression, Anxiety, Insomnia And Distress’: Mental Toll Is Extreme For Black Health Care Workerson June 25, 2020 at 6:38 am
Images in the news of racial violence, combined with the extra stress of battling a pandemic, create a toxic climate for Black health care workers. News outlets report on other stories related to ...
- Postnatal Depression: The 7 Signs to Know, Plus, How You Might Be Treatedon June 24, 2020 at 9:00 pm
In a culture that demands you perform positivity at all times, externalising your darker emotions can feel hard. When you're a new mother – and the expectation is that you're tired, sure, but largely ...
- East Pacific bursting with tropical activity as new depression formson June 24, 2020 at 11:46 am
The Eastern Pacific Ocean has sprung to life this week with forecasters tracking up to four separate areas of potential development. Of the four areas under close scrutiny, it was the tropical ...
- What's to know about managing depression during lockdown?on June 24, 2020 at 6:14 am
What are the best ways to overcome depression during quarantine? Discover tips to help support mental health during the coronavirus pandemic and lockdown.
- Teens’ Poor Sleep Tied to Later Depression, Anxietyon June 24, 2020 at 5:36 am
Teens who get very poor sleep may be more likely to struggle with poor mental health later in life, according to a new study published in the Journal of Child Psychology and Psychiatry. Researchers ...
- UCLA Anderson Forecast says U.S. economy is in "Depression-like crisis" and will not return to pre-recession peak until 2023on June 24, 2020 at 1:27 am
COVID-19, which was then still being referred to as an epidemic. Two weeks later, as the economy began shutting down because of the pandemic, the Forecast released the first revision in its 68-year ...
- Widespread storms from Southern Plains to Southeast; Subtropical depression forms in North Atlanticon June 23, 2020 at 6:03 am
The threat of severe weather returns on Tuesday for tens of millions of Americans as another tropical system has formed, continuing what has already been a busy 2020 Atlantic hurricane season.
- Subtropical depression heads northeast through Atlantic by Nova Scotiaon June 23, 2020 at 5:33 am
A subtropical depression continued to churn in the Atlantic Tuesday morning several hundred miles south of Nova Scotia, hurricane forecasters said. No other storms were expected to form within five ...
via Bing News