CBD Oil Dosis Para Dormir

CBDISTILLERY

Buy CBD Oil Online

[Cbd Oil Delivery] Cbd Gummies Lemon | LatestInWorld cbd oil dosis para dormir Best Cbd Topical, 2022-08-03 Cbd Oil Dosage For Adults cbd gummies lemon In 2020. The White cbd gummies lemon [Pure Cbd Oil] How To Mix Cbd Oil With Carrier Oil | Smokymountainsk8way.com sunday scaries gummies how much cbd Pure Cbd Oil, 2022-09-04 Organabus Cbd Oil Review how to mix cbd oil with carrier Relationships between sleep and addiction Enviar correspondencia a: Francesca Cañellas, Servei de Psiquiatria. Hospital Universitari Son Espases, C/Valldemosa n° 79. 07010 Palma de Mallorca.

[Cbd Oil Delivery] Cbd Gummies Lemon | LatestInWorld

cbd oil dosis para dormir Best Cbd Topical, 2022-08-03 Cbd Oil Dosage For Adults cbd gummies lemon In 2020.

The White cbd gummies lemon Bone Demon General did not expect that this old guy didn t panic at all in the face of the three high ranking Demon Generals, which showed that the other party had absolute confidence to fight against them.

How can you be so self willed Even if you can make such a sacrifice, the Ancient Phoenix Dynasty and cbd gummies lemon Lady Empress will not agree In Ye Fan s opinion , this time he saved the ancient Huang Dynasty completely voluntarily, Huang Linger did not need to greenhouse cbd oil make such a sacrifice.

Now that he has successfully broken through the realm and crossed the eighth level of calamity, he is already the first person under the Qingming True Immortal in Yunhai Xianmen.

It was like seeing the anger of the Great Brahma back then.

, since that s the case, don t blame me for being rude.

It is the chaotic robbery of all things misty The halo cbd vape liquid cbd gummies lemon Chaos Tribulation is not over, and the third Tribulation Cloud continues to take shape.

Don t worry, although the three of us can t defeat Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon cbd gummies lemon the Demon King Bo Xun, it s not difficult to delay the time for a stick of incense Yes.

It s amazing Uncle Ye Fan, the twelfth grade lotus platform is not ordinary.

Ye Fan is right, but the median demon general is equivalent to the true immortal of the fourth or fifth level of transcendence.

Nishang Xia Huanghu roared with tears cbd gummies lemon in his eyes.

As expected, he is the No. 1 powerhouse in the Big Dipper Galaxy.

, you ants, after all, are going to submit to the Most Effective cbd gummies lemon Lord Demon King.

Damn it, cbd gummies lemon Demon Bo Xun, cbd gummies lemon die Finally, some old powerhouses couldn t bear it any Official cbd oil dosis para dormir longer.

Boy, you have mastered such a trick, I underestimate you But even so, it is impossible to defeat the Ten Thousand Demon Blood Sacrifice The sea, with the are cbd gummies healthy power to annihilate all things, swept cbd gummies lemon towards Ye Fan from all directions.

At this moment, there are two marks on Zhou Ye s forehead.

Boom, boom, boom Within a cbd gummies lemon short period of time after the attack, the bodies of those cultivators exploded directly, and buy cbd oil cw botanicals chocolate the death was extremely tragic.

I don t know how Emperor Wu would react

Zhou Ye s legs were cbd gummies lemon already shaking, cbd oil dosis para dormir and he couldn t even control his own body, because the pressure of the other party was too great, he was like falling into Asura hell, and he was about to suffocate.

Ye Fan, cbd gummies lemon I heard that your kid is arrogant before, I thought it was just a legend, but after seeing it today, I finally understand The Demon King Bo Xun shouted angrily, causing thunder and lightning flashes in the world.

Roar, Roar Suddenly, the demons sent onslaught again.

Seeing this scene, all the Daxia cultivators were ecstatic.

Giggle, you only have to talk .

Was cbd oil pitched on shark tank?

about it, it doesn t matter, let s wait and see The cbd gummies lemon demon general did not rush to act, cbd gummies black friday in front of the three legendary tribulations.

Before the Bone Demon General. Seeing that Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon Qingming Zhenxian made a Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon move in person, Ye Fan naturally did not strive for merit, so he returned to the crowd.

After taking the Dao Enlightenment Flower and the Immortal Peach, I finally broke through to the Immortal Transformation Stage Nine.

Ye Fan saved cbd gummies lemon Xianmen from danger with one person.

Even at this most critical moment, they still have their own moral bottom line.

As soon as this woman appeared, the eyes of everyone present were cbd gummies lemon Healing Effects Of Cbd Oil uncontrollably attracted cbd gummies lemon cbd gummies lemon to her and cbd gummies lemon Healing Effects Of Cbd Oil focused on the past.

Can t you see this clearly Ah

The Most Effective cbd gummies lemon Huoxin Demon General sneered and looked at Ye Fan and the others.

There were only countless sword shadows, dazzling.

Countless cultivators cheered because they saw Official cbd oil dosis para dormir Emperor Most Effective cbd gummies lemon Xia Qin Yuan came out of the cbd gummies lemon Great Demon Array, and he came back to Xia.

What the hell is going on with these evil spirits, even Ye Fan s divine fire can t be incinerated Their bodies are very strange, what are those shining lights Many monks had doubts about these evil spirits, but they couldn t Find the key.

I m all going to cbd gummies lemon help The elders spoke in succession.

In just three days, the once prosperous Ancient Phoenix Dynasty fell apart and encountered an unprecedented catastrophe.

Because, he felt the powerful resentment and demonic energy in the Buddha Swallowing Rosary, which is also a treasure, but it has long been demonized by demonic energy.

The sword light continuously Official cbd oil dosis para dormir slashed on the dark lotus platform, but it was impossible to cbd oil dosis para dormir Customers Experience cut through the reviews on keoni cbd gummies lotus platform.

Okay, since everyone thinks this way, then you all choose elite disciples and follow cbd gummies lemon me to the core Yes Han Xiao cooperated with the others to find out from the monks that the cultivation cbd gummies lemon base was above the fifth rank of Spirit Transformation.

Suddenly, countless thunder tribulations shattered cbd gummies lemon in the sky.

In the Burial Mountain, he was recognized by the cbd gummies lemon Destiny Dragon Stone, and he was more aware of the way of Official cbd oil dosis para dormir heaven.

Very good The Demon General Huoxin nodded with legals hemp review satisfaction, and said, My servants, get cbd oil dosis para dormir Customers Experience up Obey Everyone got up one after another.

Boom The first magic light cbd gummies lemon actually shattered.

In the ancient battlefield, gods and demons fought chaotically, countless gods and cbd oil dosis para dormir Customers Experience demons, they were constantly fighting, constantly entangled, shaking the world.

don t worry about me Ye Fan just smiled and waved to Cao Yunxi, signaling her not to come over.

Because the three demon generals were too arrogant, they brought catastrophe to Yunhai Xianmen All of this made Qingming Zhenxian extremely angry Therefore, he decided to use the strongest moves to kill the enemy.

Eternal Darkness Magic Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon Light Suddenly, Demon King Bo Xun unleashed his divine might and shouted angrily.

Now that the humiliation has been completed and the goal has been achieved, Zhou Ye has no need to live.

The aura of the Demon King Bo Xun was several times stronger than before Aurora Demon Armor Seeing such a scene, the Demon Huoxin exclaimed.

At that time, it was the most terrifying time for the invasion of the demon cbd gummies lemon race.

More importantly, there is cbd gummies lemon still Shimen in my life palace Ye Fan understood, Heavenly Dao arranged this soul robbery to make him lose himself and sink Official cbd oil dosis para dormir into it forever.

No, our sword qi has been completely suppressed.

A person who can create miracles. Okay Ye Fan s face was solemn, and his brows were wrinkled.

The people who can get it are the children of destiny, born in accordance with the avenue Ye Fan, are you the destiny person of the Big Dipper Galaxy Xia Huang Qin Yuan frowned slightly, he was always there Looking for this Man best buy commonwealth 20 of Destiny, especially after the news of the invasion cbd gummies lemon of the Demon Race spread, he wanted to find such a person even more, because he knew very well that in order swags and tails to fight against this level of disaster, there must be a Man of Destiny.

It seemed like they were deliberately delaying their time.

He has the power of the bloodline of the Demon God Chi You, and fighting is his nature, but with his basic cultivation base, if he wants to open this super powerful Demon God bloodline for a long time, the price is hemp products for pain not light.

Thinking of this, everyone in the Ancient Phoenix cbd gummies lemon Healing Effects Of Cbd Oil Dynasty was depressed, and even many people shook their heads.

Zhou Ye roared in pain. He desperately tried to protect his last consciousness, but the Demon cbd effects on lungs King how many mg of cbd for sleep s power was too strong, and his spirit was instantly controlled.

This was cbd gummies lemon an unbearable humiliation, and the last thing he wanted to see.

In the nick of time, the shock changed again.

What Ye Fan was shocked, but he didn t expect Princess Nishang to be in danger.

Boom, boom, cbd gummies lemon boom In the violent explosion of magical energy, tens of thousands of Yunhai cultivators directly exploded and died, which was horrific.

, Lord White Bone, I didn t expect Lord Demon King to give you such a treasure The Drought Demon General said enviously.

Boom The whole body made a roaring sound, like Hong Zhong cbd gummies lemon Dalu, Ye Fan s foundation LatestInWorld cbd gummies lemon limit increased.

Huh Ye Fan raised his eyebrows and felt the arrow from several kilometers away.

The speed is beyond everyone s imagination.

Blood Sacrifice Demon Soldier Demon King Slash The White Bone Demon will risk his own life, Most Effective cbd gummies lemon and cbd gummies lemon the blood from his whole body will float away, constantly instilling it into the demon soldiers.

It seems that Ye Fan has been Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon able to defeat the demon general, and everything is under control.

Devil King Bo Xun, die Ye Fan was furious and flew best cbd powder up.

For a time, the entire space fell into a strange atmosphere.

Hey Ye Fan shouted angrily, and Ye Fan s whole body shone brightly, and the three magic soldiers were unsheathed at the same time.

At this time, the White Bone Demon General cbd gummies lemon cbd gummies lemon issued a cbd gummies lemon Healing Effects Of Cbd Oil kill order.

Don t be so angry, Your Royal cbd gummies lemon Highness, since I brought the army here, of cbd gummies lemon Healing Effects Of Cbd Oil Official cbd oil dosis para dormir course I want to fight and save you, but I have one condition cbd gummies lemon What condition Tell me quickly cbd gummies lemon Zhou Ye looked at Huang wellness formula tablets Linger , his eyes were full of coveted color, and he slowly said cbd full spectrum gummies 30mg It s very simple, if I can save the ancient Phoenix Dynasty, Your Highness Princess, you will marry me, okay

What Feeling that these magical instruments are unusual, the Drought Demon General now understands that Lian Yunzi was deliberately leading him into this magic circle.

At this moment, the Demon King frowned and was LatestInWorld cbd gummies lemon shocked by Ye Fan s will to fight.

Before the sect was in such a desperate situation, cbd gummies lemon it was very difficult for Cao Yunxi cbd oil public speaking to be cbd gummies lemon able to fight so firmly to the end.

It s not that he is afraid of Emperor Wu, but because cbd oil dosis para dormir Customers Experience of Qi Linglong s affairs.

These days, he has been in retreat and practiced, and he has never cbd gummies lemon come out, and everyone does cbd dosage for migraines not know his strength.

Their goal is to become the right cbd astro gummy cbd gummies lemon and cbd gummies lemon left hand of the Lord Demon, and get the gift of Lord Demon, and their strength will grow by leaps and bounds.

Those supernatural powers are extremely powerful and unbelievable.

Many of the older generation s powerhouses below also shook their heads.

Junior Brother Ye Fan, let s go Okay Zhaixingzi was in front and Ye Fan was behind, and they entered the imperial city together.

As long as Ye Fan is killed cbd gummies lemon Healing Effects Of Cbd Oil by the Yin Yang Holy Tribulation, then everything is easy to say.

He used his life essence to adopt it to you Qin Xuance Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon said.

The battlefield is the best test ground, you can see how your strength has improved.

I really didn t expect that Ye Fan s talent is so powerful that he can trigger such a catastrophe Yeah, if Ye Fan succeeds in transcending the catastrophe, it will be the first arrogance of all ages.

The only one who can rely on is Huang Linger.

Many cultivators who were about to be unable to hold on suddenly showed their eyes full of light, like a drowning person seeing a life saving straw.

But how could someone like Ye Fan be provoked by this kind of provocation Zhou Ye, I don t care what kind of magical power you used.

, Ye Fan, under cbd gummies lemon this calamity, you will cbd gummies lemon surely die Then, I won t have to take action Standing on Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon a peak, the demon of heaven LatestInWorld cbd gummies lemon will mock Ye Fan.

Bang Ye Fan s iron cbd gummies lemon Blue Label High Cbd Hemp Oil fist cbd gummies lemon slammed into her body.

The son of a thousand gold can t sit in the hall Her cbd for nervous stomach Royal Highness, let s does cbd gummies have thc leave cbd gummies lemon this task to our ten commanders.

The demon general smiled strangely, and then he stretched out his finger and touched Qin Xuance s cheek frivolously.

This is your destiny The demon general LatestInWorld cbd gummies lemon is so weak now that even carrying the magic bow feels difficult, but when he thinks about cbd gummies lemon it Ye Fan was about to die under the .

See also  Are CBD Gummies Illegal For Minors

cbd oil 24k

magic arrow, and he was ecstatic.

Huh But the middle ranked demon general just sneered, and then swung his claws, and a huge shield appeared cbd gummies help with tinnitus in front of him.

It is definitely not something they can easily resist, they must or do their best.

Ye Fan is also very strong, but although he can protect the imperial city, he is not a core member of the royal family after all.

Above other magic soldiers. Most Effective cbd gummies lemon Therefore, this arrow, killing gods and cbd gummies lemon immortals, is too terrifying.

And on Ye Fan s body, he carries the extremely pure royal road and dragon power, which makes the sun and the moon feel overshadowed by it, and everything is eclipsed by it.

Emperor Wu, you are finally here, hahaha

Emperor Wu, don t force yourself, you have done enough for everyone.

In the cemetery of the gods, Qi Linglong sacrificed herself in order Official cbd oil dosis para dormir to save Ye Fan.

Your Highness is very polite, .

How much is evolab cbd oil?

as a member of Daxia, cbd oil dosis para dormir Customers Experience this is my responsibility Ye Fan nodded slightly and said.

The graceful posture is peerless, and the blood is soaring.

do not come Ye Fan hurriedly shook his head and cbd gummies lemon shouted, if the princess took a risk and was caught by the demon general, it would be bad.

Boom Countless demons began to explode with great momentum.

I m the happiest thing to be able to see you before I die.

our demons are cruel, violent, and ruthless, but we must never be cowards A coward like you what channel is dr phil on dish is not worthy cbd gummies lemon of being a member of the demons Go to hell Alive, he is the prince of the Dayin Dynasty.

In the surrounding space, cbd gummies lemon a stream of magic cbd gummies lemon energy swayed, which made everyone s mind fall into a state of LatestInWorld cbd gummies lemon terror, and their movements slowed down.

Since you got the stele, it should be equivalent to cbd patches for hot flashes cbd gummies lemon getting all the magical powers of the stele, why can t you break through the true immortal Also, you What happened in the cemetery of the gods Qin Xuance looked curious.

The Immortal Venerable Formation LatestInWorld cbd gummies lemon Zhai Xingzi shouted, cbd gummies lemon and the seven sons of Yunhai simultaneously sent out internal energy, instilling them into the Immortal Venerable Formation.

Boom The monument appeared in speedy metals review Ye Fan s hand, and then grew wildly tall, like a mountain, standing beside Ye Fan.

This time, the Demon King failed completely.

In the Great Nether Demon cbd gummies lemon Formation, it is the Heavenly Demon that will use such a technique how long for cbd gummies to work to assist the Heavenly Demon General in battle.

Zizzizi Silk threads kept entering Ye Fan s body, dripping with cbd gummies lemon blood and bruises all over his body.

Although the ten great commanders are unparalleled, .

warfarin and cbd oil

they lack the skills to take care of hundreds .

does cvs carry cbd oil

The voice changed, and what everyone heard was really the laughter of the Heavenly Demon General.

In her eyes, there Purchase Cbd Oil From Gw Pharmaceuticals cbd gummies lemon seems to be a soul sucking power, which is very cbd gummies lemon attractive and can make people s mind sink in them instantly.

Facing the bombardment of cbd gummies lemon the demonic supernatural powers, Ye Fan did not change his face, smiled lightly, waved the phaseless sword, and slashed forward gently Ye how many drops of cbd oil should you take Fan s sword was not overwhelming, it looked very ordinary.

This is an ancient battle of gods and demons Kill Ah

The sun and the moon have no light, the black clouds are rushing away, and the sky is falling apart All the cbd oil dosis para dormir Customers Experience monks of the Cloud Sea Immortal Sect were sweating.

This cbd gummies lemon spirit made everyone awe. At this moment, everyone saw the impassioned battle of wits cbd gummies lemon from Ye cbd gummies lemon Fan .

cbd oil logan ut

s pain, and they were all conquered by Ye Fan s spirit.

Just as the two were discussing, Princess Nishang sat up from the bed, her beautiful eyes flashing with a strange brilliance, and she cbd gummies lemon stared straight at Ye Fan.

He cbd gummies lemon died in the hands of Ye Fan during the Battle of the Stars

The long sword in his hand can break the sun and the moon and break the sky Elder Xuanjizi is a soul cultivator, and his research on the soul is already well established.

Don t come here Ye Fan s cbd oil dosis para dormir Customers Experience body trembled, but he still tried his best to shout.

The joy of surviving made them admire Ye Fan cbd oil dosis para dormir Customers Experience so much.

Keng Keng Keng But these two arms were as hard as steel, with countless scales on them.

At the moment when the treasure cauldron appeared in the world, the melody continued to spread in the space.

This is the cbd gummies lemon most terrifying result for the Demon Soldiers.

In the spotlight. I saw Ye Fan holding the Dragon Stone of Destiny in his hand, and he was bathed in golden light all over his body, and the rays of light were shining brightly in the sky.

As long cbd gummies lemon as he cbd oil dosis para dormir is still cbd gummies lemon standing, the entire Big Dipper Galaxy will be saved If he knelt down, the entire Big Dipper galaxy would be defeated.

[Pure Cbd Oil] How To Mix Cbd Oil With Carrier Oil | Smokymountainsk8way.com

sunday scaries gummies how much cbd Pure Cbd Oil, 2022-09-04 Organabus Cbd Oil Review how to mix cbd oil with carrier oil Low Price.

It s too exaggerated Knowing the whereabouts of those Tiandao stones, it was flying towards the top of the mountain.

And the cemetery of the gods is so big, how could the other party come here Could it be will u test positive in a pee test while using cbd oil because of the Enlightenment Flower Suddenly, Ye Fan wanted to understand.

no matter how long they work hard, they can t get anything.

On cbd oil australia online the surface, she wanted to accept Ye Fan to enter Taiyi Gate, but who knows if she has any other ideas Therefore, Donghuang Aotian wanted to cbd oil connecticut zero thc find out what Yan Qingsi s attitude was.

At such a young royal cbd oil oklahoma law age, they could have such a firm mind and how to mix cbd oil with carrier oil understanding, even if they were in a hostile position, they had to obey.

The speed at which he drew his sword was not fast, but it implied the truth of heaven.

Linglong, he was hit hard before, now is our best chance Ye Fan said solemnly.

Huang Linger suddenly went into a rage, startling everyone.

How could such a peerless genius be defeated how to mix cbd oil with carrier oil by Tu Gang At this moment, Ye Fan smokymountainsk8way.com how to mix cbd oil with carrier oil and Tu Donghuang Aotian had his hands behind his back, his eyes were wise, as if he could cbd oil dosis para dormir see through everything.

Therefore, she covered her how to mix cbd oil with carrier oil perfect face just to concentrate on her cultivation.

As the Destiny sunday scaries gummies how much cbd Shop Dragon continued to scream in pain, the dharma was sunday scaries gummies how much cbd Shop broken, Ye Fan regained his original form, and then body sh n quickly retreated, like a kite with a broken string falling.

From the moment smokymountainsk8way.com how to mix cbd oil with carrier oil he was born, he became the holy son of Taiyi.

After a while, Emperor Xia also returned to his throne, smokymountainsk8way.com how to mix cbd oil with carrier oil and the power of the emperor spread out, like an buy cbd gummies amazon emperor patrolling the territory, and ten thousand people bowed their heads Huh There are six emperors here, but the one from the Great Wu Dynasty hasn t come yet Suddenly, someone shouted.

No one can be completely how to mix cbd oil with carrier oil unmoved by a beauty like Princess Nishang.

It is the root of how to mix cbd oil with carrier oil Benefits Of Cbd Oil how to mix cbd oil with carrier oil his all powerful sunday scaries gummies how much cbd Shop power during his lifetime.

The power of naturals aultra cbd oil is it tested through a third party this golden light shield continued to increase, gradually isolating the invasion how to mix cbd oil with carrier oil of the magic sound.

Victory or defeat, life or death, you Benefits Of Cbd Oil how to mix cbd oil with carrier oil can only see Ye Fan s own creation

Broken It s just a simple word, the god tablet condenses the heavenly shield, and Gangfeng can t invade.

At this moment, there is only a catastrophe between heaven and earth, and no life is left I didn t expect that my famous name, Qi Hong, how to mix cbd oil with carrier oil Cbd Oil For Rls would die in a catastrophe Suddenly, a look of What Does Cbd Do sunday scaries gummies how much cbd despair appeared on Qi cbd oil for rheumatoid arthritis holland and barrett Hong s face.

Boom The giant seal slammed into the sky, and the robbery cloud in the air instantly vet cbd dosage dissipated and disappeared, as if it had never appeared before.

Emperor Feng, the situation was special at that time, the demons were extremely powerful, and the major dynasties smokymountainsk8way.com how to mix cbd oil with carrier oil had already done their best Xia Huang said.

Suddenly, Ye Fan stopped smokymountainsk8way.com how to mix cbd oil with carrier oil again. Huh Suddenly, he found that there was a mysterious power awakening in his body, which resonated with the summoning power of the Stone King.

Ye Fan didn t know how much distance he had run, but even though Nan Yutian was severely injured, his speed was still how to mix cbd oil with carrier oil extremely fast and he couldn how to mix cbd oil with carrier oil Benefits Of Cbd Oil how to mix cbd oil with carrier oil t get rid how to mix cbd oil with carrier oil of it.

A layer of pale golden scales. These scales seem to be integrated how to mix cbd oil with carrier oil with the marjuana gummies what is the meaning of variety skin and are very harmonious.

For him, it was a very unpleasant thing to miss the flower of enlightenment.

His speed is too fast. So feel it with your heart With your heart You are so talented, do you want me to teach you Okay Ye Fan nodded.

The colorful haze cauldron and the Taiyi cbd oil gummies to stop smoking golden sword shattered one after another.

, then come on Zhou Ye swung the ancient emperor sword, and the powerful sword energy directly attacked the old prince.

Humph Li Feng, you overestimate your own strength, I will win this match Princess Nishang retorted.

Although they are not convinced, they are very clear in their hearts Although many cultivators how to mix cbd oil with carrier oil are not so strong, their eyes are very strong.

One hit kills Donghuang Aotian didn t want to give Ye Fan any chance cbd oil warts to breathe.

Come. Boom Donghuang Aotian seemed to have been hit by ten thousand thunderbolts, and he had no strength to fight back, and was completely knocked out.

Instead, it directly broke the illusion of this king Qi Hong s state of mind is really good.

Ye Fan, look good. Donghuang Aotian s palm strength burst, and the palm strength infused with immortal power was like a beast coming out of its cage, extremely powerful, and attacked Ye Fan.

But he never imagined that the python could evolve for the sunday scaries gummies how much cbd Shop tenth time when it came in.

However, no Tianjiao cbd oil for menstrual cramps was blessed by the god is cbd oil federally legal tablet again, so how to mix cbd oil with carrier oil that everyone s worship of Qin Xuance was even Benefits Of Cbd Oil how to mix cbd oil with carrier oil more obvious.

At this moment, Ye Fan frowned and did how to mix cbd oil with carrier oil not answer.

is it the blood of Split Sky Si Qi Linglong s light flashed, and it seemed that he had found the source of the subtle changes in his body.

To tell you the truth, the troops I lead are only the vanguard After that, there are a total of twelve upper ranking demon generals, 81 middle ranking demon generals, 360 lower ranking demon generals, and billions of demons.

He was standing on the head of the giant dragon high .

What is the purest cbd oil I can get?

in the sky, the sword in his hand exuded an extremely dazzling light, and then fell at Zheng Qifeng.

What, but to be sunday scaries gummies how much cbd Shop on the safe side, she still wanted to ask.

If it wasn t for the age of 100, I how to mix cbd oil with carrier oil would want to enter the knot.

1 Tianjiao, but he also knew very well in his heart that Qi Linglong s strength was far above him, but as a daughter body sh n , he was not known.

After all, she was from the Holy Land of Taiyi, and it was impossible to Benefits Of Cbd Oil how to mix cbd oil with carrier oil defend Ye Fan.

The strongest Tianjiao, only in this way can he recognize his master and be willing to be picked by you Hearing Wei Lao how to mix cbd oil with carrier oil s cbd oil keeping me awake words, Ye Fan realized smokymountainsk8way.com how to mix cbd oil with carrier oil What Does Cbd Do sunday scaries gummies how much cbd that Wudaohua also wanted to follow the strongest master, wholesale bulk cbd oil and since that was the case, he naturally Will not give in.

The blow just now was extremely powerful.

There are such treasures. This way, it will be much easier for their direct disciples to come to the Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil Burial Mountain to find the Heavenly Dao Stone.

See also  Organic Full Spectrum CBD Oil Uk

The most nervous are the Dayin Dynasty and the Kamikaze Dynasty.

And high purity natural products complaints the powerhouses of the major dynasties and the arrogances of the sky have set off smokymountainsk8way.com how to mix cbd oil with carrier oil a huge wave in their hearts, and they are beyond surprised.

Zheng Just when Ye Fan was Benefits Of Cbd Oil how to mix cbd oil with carrier oil about cbd oil hobart to lose his hold, he heard a harsh voice resounding through does cbd oil pop on a drug test the audience.

Seeing everyone in such how to mix cbd oil with carrier oil a state, Ao Zhan s eyebrows were tightly locked.

The latter nodded slightly, and total gym 1500 exercise sunday scaries gummies how much cbd Shop then walked to the Qiqiao Linglong Stone.

Hey Stop talking how to mix cbd oil with carrier oil Cbd Oil For Rls nonsense, let s welcome your death Qi Linglong concentrated, at this how to mix cbd oil with carrier oil moment, she Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil couldn t have any distracting thoughts, whether it was Ye Fan or Split Sky Si no longer existed, she was the only one here.

Ye Fan, since you ve made up your mind, I can only bless you.

Suddenly, Ye Fan turned to look at Ao Zhan, and said loudly, Senior Ao Zhan, according how to mix cbd oil with carrier oil to the rules of the God Monument Festival, you can t cbd gummies for kids near me kill people But cbd oil for globus sensation now, as Shang Bin is a dog of the how to mix cbd oil with carrier oil Dawu Dynasty, killing him should not be considered a violation.

The closer you get to the top, the greater the pressure This kind of pressure will gradually transform into the coercion of heaven, which will make the comers fear and even be severely injured.

When Ye Fan heard this, his heart skipped a beat.

last blow. Look, it s actually Ye how to mix cbd oil with carrier oil Fan What Why is he still on the battlefield Why did he appear in front of how to mix cbd oil with carrier oil Qi Hong, isn t he afraid of the power of heaven bi bi , a huge wave was set off in my heart, and I was beyond surprised.

I really lost my identity Tu Gang sneered, his eyes full of ridicule, sunday scaries gummies how much cbd Shop thinking.

You, what did you say He may have waited for the power of Enlightenment Flower to be fully released, and then took Enlightenment Flower to increase his strength to fight the pressure of the peak This is impossible How powerful is Enlightenment Flower Only the most amazing and brilliant Tianjiao can take such how to mix cbd oil with carrier oil ancient treasures If they are not qualified enough, they will not be able to withstand the energy, and they will explode and die Back then, that Immortal Venerable took the Enlightenment Flower and was promoted He is an Immortal Emperor, but if you change to a Tribulation Transcendence cultivator, I am afraid that how to mix cbd oil with carrier oil you how to mix cbd oil with carrier oil will have a life threatening worry And this kid is only a rank eight rank god, and taking the Dao Enlightenment Flower is equivalent to how to mix cbd oil with carrier oil Cbd Oil For Rls courting death Donghuang Aotian .

using cbd oil

said coldly, Looking at Ye Fan s eyes like a corpse.

, come on, come on, let me witness the stalwart of the power of heaven and earth Qi Hong laughed, his whole body sh n emitting sunday scaries gummies how much cbd Shop golden light, just like a golden armored war god, how to mix cbd oil with carrier oil Cbd Oil For Rls this is his body protection holy light.

This was a scene Nan Yutian never expected.

Such terrifying energy fluctuations shook and distorted the surrounding space.

Ah He screamed, almost falling from the sky.

Damn Ye Fan was furious in his heart, but he was the one who got the destiny s true dragon stone.

He had been interested in Princess Nishang for a long time, but after Qi Linglong showed his true face, he moved away.

Zhou Ye, that s enough Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil Suddenly, a voice shook the audience, and the prince Qin Xuance of the Great Xia Dynasty stood up.

It s too much Suddenly, Elder Wei exclaimed.

Although he was very arrogant, he was still unable to how to mix cbd oil with carrier oil face the power of Immortal Venerable What Does Cbd Do sunday scaries gummies how much cbd Law.

Ye Fan, be careful Princess Nishang shouted to Ye Fan when she saw the attack direction of the magic knife.

The What Does Cbd Do sunday scaries gummies how much cbd mighty power of flames emanated overwhelmingly, causing a sea of flames to form in the entire sky.

The battle between the two princes did not cause this ancient battlefield to be turned sunday scaries gummies how much cbd Shop upside down, because their grasp of power has reached a state of perfection, and they poured as much how to mix cbd oil with carrier oil power on each other cbd oil for anger as possible.

Boom boom boom The breath of the undead peach became stronger.

Yan Qingsi didn t want to have any more problems.

Ye Fan, you bastard, speak up Zhou Ye couldn t bear it anymore.

And here, the final round of the competition of the God Stele Festival is about to start.

Medium burn. My lord, how to mix cbd oil with carrier oil I am indeed playing on behalf of Daxia, but how to mix cbd oil with carrier oil as you all saw, Qi Hong is too scary, Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil what s the use of me It s just being tortured I want to Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil preserve my strength and participate in the next Divine Stele Festival Yes Come on, haven t you always admired Ye Fan before, now go to him, come to him Shang Bin s words made everyone angry, especially Princess Nishang, who just saw stash cbd gummies sugar hi 20gm Gao Yuan fight to the last drop of blood for Da Xia, but now Shang Bin is actually afraid of the battle, which is a cbd living gummies shame for Da what is cannabinoid oil Xia.

Everyone was surprised when such a thing happened.

fair How is this .

What is best cbd oil for pain?

how to mix cbd oil with carrier oil fair Clearly a one sided massacre This time, Zhou Ye wanted to show off his skills and cbd for body pain show the majesty of himself and the Dayin Dynasty, but is there any evidence that topical cbd oil releives pain he didn t expect to be suppressed by Ye Fan in all aspects, and even he was defeated by Ye Fan.

East Emperor Aotian, how to mix cbd oil with carrier oil I also want to tell you that a divine object has a spirit, and you seek its own owner Even if you find a Tiandao stone with a lot of Taoism, it doesn t mean that you can take it away, you must get the approval of the Tiandao stone.

Emperor Xia doesn t need to be too polite.

Kill The demon general issued a kill order, and a large number of demon warriors rushed towards the forces of the major dynasties below.

Admit it, and sunday scaries gummies how much cbd Shop this is above how to mix cbd oil with carrier oil Yinghuo Xing, everything must follow the rules of the God Stele Festival.

Qin Xuance s tenfold improvement is equivalent to other people s cultivation for a hundred years.

For zen pro cbd how to mix cbd oil with carrier oil a time, the situation changed, the sky collapsed and the earth cracked, the universe reversed, how to mix cbd oil with carrier oil and the heaven and the earth shook That kind of destructive who can sell cbd oil in missouri power like God s punishment is too terrifying.

You how to mix cbd oil with carrier oil are thinking too much Suddenly, how to mix cbd oil with carrier oil Cbd Oil For Rls Ye Fan s eyes emitted an extremely powerful flame of king harvest cbd oil light.

At this moment, Ye Fan was climbing towards the top of the how to mix cbd oil with carrier oil Cbd Oil For Rls mountain.

Now that how to mix cbd oil with carrier oil my body has recovered to its best state, it s time to take the Enlightenment Flower He took out the Enlightenment Flower and found that the light above was smokymountainsk8way.com how to mix cbd oil with carrier oil even more flaming, and even triggered the vision of heaven and earth is cbd oil good for eczema again.

Wei, I understand This time, Ye Fan nodded cooperatively, and then looked at Glancing sunday scaries gummies how much cbd at Qi Linglong, that beautiful face, even in a state of sleep, can still make Ye Fan s mind sway.

I will thank you for your efforts and let you and I be forever Ye Fan raised the enlightenment flower high, Just about to take how to mix cbd oil with carrier oil it.

Boom Just as how to mix cbd oil with carrier oil the magic soldiers and the magic soldiers were at a stalemate, the blood of the gods on the ancient spear instantly stimulated their full potential.

Not only that. Her own vitality was also draining how to mix cbd oil with carrier oil Cbd Oil For Rls wildly, as if she had been completely overdrawn, and not a how to mix cbd oil with carrier oil drop was left.

Take action to punish this bastard. Now, he still wants to get the chance to try the god tablet, which is ridiculous.

We cbd oil cheapest don t have much time, so we have to carry out the how to mix cbd oil with carrier oil how to mix cbd oil with carrier oil mission of the division Yes, how to mix cbd oil with carrier oil Cbd Oil For Law Enforcement the duration of the how to mix cbd oil with carrier oil space time passage must be limited.

He asked word by word, Senior how to mix cbd oil with carrier oil Ao Zhan, since you said that I am the second Then who is the first Want to know the answer.

Ao Tian of the Wanlong how to mix cbd oil with carrier oil Dynasty. said very rudely.

Boom The powerful blood pact forbidden technique roared out, attacking Sky Splitting.

These palm strengths came directly from which mountain peaks, without giving Qin Xuance any preparation What Does Cbd Do sunday scaries gummies how much cbd time.

But the magic knife seems to have a spirit and can identify its own target.

Whoosh In an cbd oil and eye pressure instant, Ye Fan What Does Cbd Do sunday scaries gummies how much cbd entered the swallowing nebula.

After pondering for a does cbd oil store in the body and showup in drug test moment, as if she had experienced a battle between heaven and man, Huang Linger s beautiful eyes dimmed, and she murmured, Ye Fan, I m sorry It is very difficult to be able to help to such an extent that they met by chance.

At this moment, on .

erth hemp banana cbd oil tincture

a mountain, Ye Fan and the three stood how to mix cbd oil with carrier oil cbd oil topicals still.

That simple finger actually broke open his prison, and at the same time shook smokymountainsk8way.com how to mix cbd oil with carrier oil back countless heroic souls in the ancient battlefield.

Although it is not a holy beast, it is also extremely terrifying, and how to mix cbd oil with carrier oil it can be compared with the monks of the seventh or eighth level of tribulation.

Not only the cultivator .

cbd oil cancer reviews

s sunday scaries gummies how much cbd Shop breakthrough, but also the birth of the divine pill and the divine weapon will also trigger thunder tribulation.

Those who reach the Tao are the vehicles.

However, smokymountainsk8way.com how to mix cbd oil with carrier oil even if his own hemp oil with cbd gummies soul is sunday scaries gummies how much cbd Shop destroyed, Qi Linglong will not be hurt in the slightest Qi Linglong spent a huge price to display the strongest forbidden technique, and an irresistible force of destruction instantly erupted.

After all, they have an Immortal Venerable over there, and the Immortal Venerable of Yunhai Xianmen has fallen for thousands of years, so naturally all kinds of magical powers cannot be passed on.

They have long been unknown where they are, and they have cultivated to an unimaginable level, and even entered a more advanced how to mix cbd oil with carrier oil level.

At the same time, the does cbd oil help heal your gut nine Dao Yun within the stone king released unprecedented power, which how to mix cbd oil with carrier oil flew out directly, condensed into substance, and surrounded the princess of how to mix cbd oil with carrier oil the god race, adding the bio cbd plus ultimate brilliance to should i buy oil her.

Moderate, according sunday scaries gummies how much cbd Shop to their talent, they may be able to persevere to the end.

Between life and death, Dongfang Mingyue gave his .

How often should you dose with cbd oil?

Phoenix blood essence to Ye Fan, thus giving him the fire of Nirvana.

Trauma is easy to recover, but the damage to the internal organs and even the dantian cannot be completely recovered within a .

How long until cbd oil takes effect?

I, I, never like to owe favors Since you protected me just now, now, it s up to how to mix cbd oil with carrier oil me.

She felt Qin Xuance s defeat. Humph Even if no one believes that I can win, I will fight against the sky This is me This is the prince of the Great Xia Dynasty Qin Xuance Benefits Of Cbd Oil how to mix cbd oil with carrier oil Even if you Benefits Of Cbd Oil how to mix cbd oil with carrier oil lose, even if you die , I want this name to resound through the Big Dipper Qin Xuance s roar resounded throughout the ancient battlefield.

See also  Best CBD Oil For Migraines

She has a faint hunch that Ye Fan is too mysterious, maybe

This is how to mix cbd oil with carrier oil too exaggerated Indestructible Divine Body Once the cultivation reaches the realm of Dacheng, Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil the diamond will not be destroyed, the sword will not Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil be penetrated, and it will not be destroyed.

Boom Suddenly, with the completion of the unsealing of the cinnabar seal, a terrifying aura emerged.

Such a strange place, it s terrifying Qi Linglong s heart trembled violently, and the more he urged the power of the ark to protect himself.

He approached slowly and saw an extremely delicate face.

This kind of talent, even Ye Fan how to mix cbd oil with carrier oil was shocked, and can definitely kill any Tianjiao in Beidou.

At this moment, an abrupt female voice suddenly sounded from behind.

It was covered Thc Free Cbd Oil Lucky Vitamin how to mix cbd oil with carrier oil with the blood of the Golden Dragon.

Please don t how to mix cbd oil with carrier oil misunderstand me. Ye Fan stepped how to mix cbd oil with carrier oil forward and grabbed the princess.

At this moment, the forces of the two smokymountainsk8way.com how to mix cbd oil with carrier oil sides were how to mix cbd oil with carrier oil constantly fighting each other, creating countless bursts of power in the sky, and the cultivators could not take their eyes off of them, but they were trembling, for fear that they would be affected by these forces and die here.

His goal was to find a high level Tiandao Stone, and he no longer had much interest in the battle between the two.

Do you still want to hide this kind of conspiracy and tricks The sunday scaries gummies how much cbd Shop old man of the Dayin Dynasty stood up.

As runners up, their seats are second only to the Great Xia Dynasty.

Kill The two people s shouts of killing shook the world, and the sound of the collision between Wuhuangdao and Wuxiangjian smokymountainsk8way.com how to mix cbd oil with carrier oil was endless.

Yan Qingsi, why can sunday scaries gummies how much cbd t you defend this kid today, this is a bet between Ye Fan and I, what does it have to do with you how to mix cbd oil with carrier oil Facing Yan Qingsi s questioning, Tu Gang was actually very empty inside, after all This how to mix cbd oil with carrier oil bet can be said to be extremely unfavorable to Ye Fan at first glance, and it can almost be said to be a dead end.

Relationships between sleep and addiction

Enviar correspondencia a: Francesca Cañellas, Servei de Psiquiatria. Hospital Universitari Son Espases, C/Valldemosa n° 79. 07010 Palma de Mallorca. España, [email protected] – Tel: +34871206673

Resumen

La interacción entre los trastornos del sueño y el abuso de sustancias es ya conocida, pero seguramente más compleja de lo que se pensaba. Existe tanto una relación positiva entre tener un trastorno por uso de substancias y sufrir un trastorno de sueño, como viceversa. Los efectos sobre el sueño dependen de la substancia utilizada, pero se ha demostrado que tanto durante su uso como en período de abstinencia los consumidores tienen diferentes problemas de sueño y fundamentalmente un sueño más fragmentado. Sabemos que hay que tener en cuenta los problemas de sueño para evitar recaídas en la adicción.

Investigaciones recientes indican que el sistema hipocretinérgico definido por el neuropéptido hipocretina/orexina (Hcrt/ox), localizado en el hipotálamo lateral e implicado entre otros en la regulación del ciclo sueño-vigilia, jugaría un papel importante en las conductas adictivas. Diferentes estudios han demostrado interacciones entre el sistema hipocretinérgico, los circuitos de respuesta aguda al estrés y los sistemas de recompensa. También sabemos que la activación optogenética selectiva del sistema hipocretinérgico incrementa la probabilidad de la transición del sueño a la vigilia, y también es suficiente para iniciar un comportamiento compulsivo de recaída adictiva. La activación del sistema hipocretinérgico podría explicar la hipervigilia asociada al estrés y a la adicción. El mayor conocimiento de esta interacción permitiría entender mejor los mecanismos de la adicción y encontrar nuevas estrategias para el tratamiento de las adicciones.

Abstract

While it is well known that there is an interaction between sleep disorders and substance abuse, it is certainly more complex than was previously thought. There is a positive relationship both between having a substance use disorder and suffering from a sleep disorder, and vice versa. The effects on sleep depend on the substance used, but it has been shown that both during use and in withdrawal periods consumers have various sleep problems, and basically more fragmented sleep. We know that sleep problems must be taken into account to prevent addiction relapses.

Recent research shows that the hypocretinergic system defined by neuropeptide hypocretin/orexin (Hcrt/ox), located in the lateral hypothalamus and involved in, among other things, the regulation of the sleep-wake cycle, may play an important role in addictive behaviors. Different studies have demonstrated interactions between the hypocretinergic system, acute response to stress circuits and reward systems. We also know that selective optogenetic activation of the hypocretinergic system increases the probability of transition from sleep to wakefulness, and is sufficient for initiating an addictive compulsive behavior relapse. Hypocretinergic system activation could explain the hyperarousal associated with stress and addiction. Improved knowledge of this interaction would help us to understand better the mechanisms of addiction and find new strategies for the treatment of addictions.

La interacción entre los trastornos del sueño y el abuso de sustancias es compleja. Hasta hace poco conocíamos una relación bidireccional positiva entre el riesgo de tener un trastorno por uso de substancias y sufrir un trastorno de sueño: las personas con abuso o dependencia de sustancias tienen mayor prevalencia de alteraciones del sueño y las que presentan alteraciones del sueño tienen mayor riesgo de presentar problemas relacionados con el uso de sustancias que la población general (Cañellas et al., 1998; Ford y Kamerow, 1989).

Investigaciones recientes apuntan que la interacción entre adicciones y niveles de vigilancia es más compleja. El ciclo vigilia sueño esta regulado por un conjunto de redes neuronales que controlan diferentes aspectos de la transición entre los diferentes estados de vigilancia. En concreto, el sistema definido por el neuropéptido hipocretina/orexina (Hcrt/ox), localizado en el hipotálamo lateral (de Lecea et al., 1998; Sakurai et al., 1998), juega un papel crucial en la estabilidad del ciclo, ya que su deficiencia da lugar a la narcolepsia con cataplejía (Hungs y Mignot 2001). El sistema Hcrt está implicado en el control de numerosas variables, como el estado metabólico, ritmo circadiano, duración previa del sueño, niveles de estrés, etc. y transmite esta información de forma integrada a otros circuitos esenciales para el mantenimiento de la vigilia (Sutcliffe y de Lecea, 2002).

La implicación tan significativa del sistema hipocretinérgico en la vigilia llevó a la hipótesis de un posible papel de este circuito en la hipervigilia asociada al estrés y la adicción, como describiremos más adelante.

Acción de las principales drogas sobre el sueño

En el estudio ECA (Ford y Kamerow, 1989) se describió que los pacientes que referían preocupaciones sobre el sueño tenían un riesgo relativo 2.32 veces mayor de desarrollar problemas relacionados con el alcohol, detectándose especialmente en los que presentaban historia de ansiedad y disforia. Aunque también se ha descrito esta relación con otras sustancias, la mayoría de los estudios han sido realizados en alcohólicos (Irwin et al. 2006). El insomnio, en la adolescencia, está relacionado con el desarrollo posterior de trastornos mentales, asociándose al uso de alcohol, cannabis, otras drogas, depresión y a ideas e intentos de suicidio. Además, el insomnio es más frecuente en los adolescentes, que fuman, beben y duermen menos tiempo durante el fin de semana (Roane et al., 2008).

Aunque las acciones sobre el sueño dependen de la droga consumida, y el objetivo de esta editorial no es repasar detalladamente cuales son específicamente estas alteraciones, nos detendremos a señalar algunas que son características y frecuentes, debido a su importancia en el manejo de los pacientes con trastorno del uso de substancias.

La mayoría de estudios se han realizado con el alcohol, que es el ansiolítico e hipnótico más ampliamente utilizado en el mundo occidental desde hace milenios. En consumo agudo esta sustancia ejerce un efecto inductor del sueño, pero en consumo continuado deteriora su calidad, problema que se agrava todavía más durante el periodo de abstinencia. A dosis bajas, como podría ser el consumo social reconocido como “normal” en los países latinos, con unos niveles plasmáticos de alcohol bajos, no tiene claros efectos sobre la arquitectura del sueño. A dosis más altas produce un efecto similar al de un hipnótico de acción corta: disminuye la latencia de sueño, así como los despertares, la fase de sueño 1 y la densidad de movimientos oculares rápidos (REM) en la primera mitad de la noche; mientras que en la segunda mitad se aprecian fenómenos de rebote con aumento de la fase de sueño 1, aumento de despertares y un incremento de sueño REM. En pacientes alcohólicos crónicos, se ha encontrado una disminución del sueño lento profundo, del sueño REM y un sueño más fragmentado. Durante la fase de abstinencia estas alteraciones se agravan. Los sujetos duermen menos, el sueño está más fragmentado y tienen una disminución del sueño lento, mientras que la duración del REM y la densidad de los movimientos oculares rápidos están incrementadas (Brower et al., 2011). De hecho, uno de los factores de recaída en el consumo de alcohol, tras un periodo de abstinencia puede ser la persistencia de alteraciones del sueño. Por ello se recomienda dar inductores del sueño durante la fase de abstinencia aguda y, si el insomnio persiste, utilizar antidepresivos sedativos como la trazodona, para mejorar la calidad de sueño y prevenir las recaídas (Kolla et al 2011).

En un trabajo reciente, realizado por el equipo de Roncero (2011) en una unidad de desintoxicación, se resumen los diferentes efectos sobre el sueño de diferentes substancias y en periodo de abstinencia. Los estimulantes disminuyen la sensación de necesidad sueño, en muchas ocasiones los pacientes no tienen la percepción subjetiva de alteración del sueño o sueño no reparador. La cocaína tiene un efecto euforizante sobre el ánimo, disminuye el tiempo total del sueño y altera su continuidad. Durante el periodo de abstinencia o disminución del consumo regular, aumenta el tiempo total de sueño y la somnolencia diurna.

El consumo de cannabis a dosis altas disminuye el sueño REM y el sueño de ondas lentas. El uso de cannabis también se relaciona con el aumento del número de movimientos periódicos de las extremidades durante el sueño y sueño más fragmentado. La abstinencia de cannabis reduce la calidad del sueño, aumenta la latencia y produce sueños extraños. La abstinencia después de la exposición de 4–5 cigarrillos/día, incluso tras un período corto, se ha asociado con aumento de la latencia y de la fase REM.

Los opioides producen reacciones de alertamiento dependientes de la dosis, con aumento de la actividad muscular medida en el EMG y de los movimientos corporales. El EEG muestra un aumento de la actividad alfa, y una disminución de las fases de sueño lento profundo y del sueño REM. Los sujetos en tratamiento agudo con metadona, refieren dormir mejor. Muestran un discreto aumento del sueño lento profundo y una disminución de las frecuencias EEG rápidas durante el sueño. Durante la fase de administración crónica de metadona el sueño nocturno no esta alterado, aunque un porcentaje de pacientes refiere insomnio de conciliación y mantenimiento. Durante las primeras 3–5 semanas de abstinencia los sujetos refieren un aumento de la actividad onírica e insomnio. Durante la abstinencia de opiáceos en dependientes, aumentan los sueños y la fase REM y delta. Tras la retirada, se describe un periodo de insomnio de varias semanas de duración. El insomnio persistente puede provocar una recaída en el consumo de heroína.

Relación Entre Los Circuitos Neuronales de Recompensa y Ciclo Vigilia/Sueño

Estudios neuroanatómicos y electrofisiológicos han demostrado interacciones entre el sistema hipocretinérgico y los circuitos de respuesta aguda al estrés (Winsky-Sommerer et al., 2004). Asimismo, estudios en ratas demostraron que la aplicación farmacológica de Hcrt-1 era suficiente para inducir una recaída adictiva (Boutrel et al., 2005). Una literatura ya abundante demuestra que, en efecto, existe una importantísima relación entre el sistema hipocretinérgico con el sistema dopaminérgico mesocorticolímbico. También contribuyen a esta interacción con los sistemas de recompensa, los circuitos hipotalámicos adyacentes (p.ej, neuronas que contienen MCH (hormona concentradora de melanina), neurotensina o sensibles a leptina (lepRB).

Recientemente estudios optogenéticos en roedores han permitido establecer relaciones causales entre la actividad de circuitos neuronales y comportamientos complejos. Así, la activación optogenética selectiva del sistema hipocretinérgico, incrementa la probabilidad de la transición del sueño a la vigilia (Adamantidis el al., 2007), y también es suficiente para iniciar un comportamiento compulsivo de recaída adictiva. Como decíamos en los apartados anteriores, la literatura ha revelado numerosas asociaciones entre el abuso de drogas y deficiencias clínicas en la arquitectura del sueño. Por otra parte, varios estudios clínicos han mostrado que los pacientes narcolépticos deficientes en Hcrt, que reciben dosis frecuentes de psicoestimulantes (anfetaminas, metilfenidato o modafinil) para el tratamiento de la somnolencia diurna excesiva, son relativamente resistentes a la adicción.

El papel del sistema hipocretinérgico en la adicción sería el de actuar conjuntamente con el sistema dopaminérgico y añadir un valor positivo a la recompensa (de Lecea et al., 2006). La activación del sistema dopaminérgico puede tener consecuencias en el papel de las neuronas hipocretinérgicas durante el sueño, ya que controlan la generación del ritmo theta en el hipocampo y facilitan las transiciones sueño vigilia. Esto explicaría porqué los pacientes adictos muestran un sueño fragmentado con múltiples despertares nocturnos.

Además de la interacción Hcrt-dopamina, hay otros circuitos compartidos entre la regulación del estado de vigilia y la recompensa cerebral. En concreto, la actividad del sistema noradrénergico del locus coeruleus, esta altamente correlacionada con los estados de vigilia e inversamente proporcional al sueño (Aston-Jones y Shipley, 1987). También el sistema serotonérgico es importante para la regulación de la entrada en sueño REM, y contribuye de forma notable como neuromodulador en el estado de animo en general y en conductas adictivas.

Cabe señalar que el ciclo vigilia sueño se manifiesta a través cambios de actividad globales de la corteza cerebral en el electroencefalograma. Además, los circuitos de motivación y recompensa convergen en la corteza prefrontal. Así pues también hay mecanismos de control “bottom-up” que comparten las transiciones de sueño a vigilia y las de vigilia a hipervigilia. Es de esperar que cuando se establezcan nuevas implicaciones de circuitos neuronales en el comportamiento adictivo, se revelen también nuevas asociaciones con las redes neuronales responsables de la regulación del ciclo de sueño vigilia. El mayor conocimiento de esta interacción permitiría entender mejor los mecanismos de la adicción y encontrar nuevas estrategias para el tratamiento de las adicciones (Plaza-Zabala, Maldonado y Berrendero 2012).

Footnotes

Conflicto de intereses

Los autores declaran no tener ningún conflicto de intereses en esta publicación.

How useful was this post?

Click on a star to rate it!

Average rating 5 / 5. Vote count: 1

No votes so far! Be the first to rate this post.